| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Alamiri, Feiruz, et al.
(författare)
-
Role of serotype and virulence determinants of Streptococcus pyogenes biofilm bacteria in internalization and persistence in epithelial cells in vitro.
- 2023
-
Ingår i: Frontiers in cellular and infection microbiology. - 2235-2988. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes causes a multitude of local and systemic infections, the most common being pharyngitis in children. Recurrent pharyngeal infections are common and are thought to be due to the re-emergence of intracellular GAS upon completion of antibiotic treatment. The role of colonizing biofilm bacteria in this process is not fully clear. Here, live respiratory epithelial cells were inoculated with broth-grown or biofilm bacteria of different M-types, as well as with isogenic mutants lacking common virulence factors. All M-types tested adhered to and were internalized into epithelial cells. Interestingly, internalization and persistence of planktonic bacteria varied significantly between strains, whereas biofilm bacteria were internalized in similar and higher numbers, and all strains persisted beyond 44 hours, showing a more homogenous phenotype. The M3 protein, but not the M1 or M5 proteins, was required for optimal uptake and persistence of both planktonic and biofilm bacteria inside cells. Moreover, the high expression of capsule and SLO inhibited cellular uptake and capsule expression was required for intracellular survival. Streptolysin S was required for optimal uptake and persistence of M3 planktonic bacteria, whereas SpeB improved intracellular survival of biofilm bacteria. Microscopy of internalized bacteria showed that planktonic bacteria were internalized in lower numbers as individual or small clumps of bacteria in the cytoplasm, whereas GAS biofilm bacteria displayed a pattern of perinuclear localization of bacterial aggregates that affected actin structure. Using inhibitors targeting cellular uptake pathways, we confirmed that planktonic GAS mainly uses a clathrin-mediated uptake pathway that also required actin and dynamin. Clathrin was not involved in biofilm internalization, but internalization required actin rearrangement and PI3 kinase activity, possibly suggesting macropinocytosis. Together these results provide a better understanding of the potential mechanisms of uptake and survival of various phenotypes of GAS bacteria relevant for colonization and recurrent infection.
|
|
| 6. |
- Amer, Ayad, et al.
(författare)
-
YopN and TyeA Hydrophobic Contacts Required for Regulating Ysc-Yop Type III Secretion Activity by Yersinia pseudotuberculosis
- 2016
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Yersinia bacteria target Yop effector toxins to the interior of host immune cells by the Ysc-Yop type III secretion system. A YopN-TyeA heterodimer is central to controlling Ysc-Yop targeting activity. A + 1 frameshift event in the 3-prime end of yopN can also produce a singular secreted YopN-TyeA polypeptide that retains some regulatory function even though the C-terminal coding sequence of this YopN differs greatly from wild type. Thus, this YopN C-terminal segment was analyzed for its role in type III secretion control. Bacteria producing YopN truncated after residue 278, or with altered sequence between residues 279 and 287, had lost type III secretion control and function. In contrast, YopN variants with manipulated sequence beyond residue 287 maintained full control and function. Scrutiny of the YopN-TyeA complex structure revealed that residue W279 functioned as a likely hydrophobic contact site with TyeA. Indeed, a YopNW279G mutant lost all ability to bind TyeA. The TyeA residue F8 was also critical for reciprocal YopN binding. Thus, we conclude that specific hydrophobic contacts between opposing YopN and TyeA termini establishes a complex needed for regulating Ysc-Yop activity.
|
|
| 7. |
- Andersson, Tilde, et al.
(författare)
-
Development of a Molecular Imprinting-Based Surface Plasmon Resonance Biosensor for Rapid and Sensitive Detection of Staphylococcus aureus Alpha Hemolysin From Human Serum
- 2020
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Stapylococcus aureus is a common infectious agent in e.g. sepsis, associated with both high mortality rates and severe long-term effects. The cytolytic protein α-hemolysin has repeatedly been shown to enhance the virulence of S. aureus. Combined with an unhindered spread of multi drug-resistant strains, this has triggered research into novel anti virulence (i.e. anti α-hemolysin) drugs. Their functionality will depend on our ability to identify infections that might be alleviated by such. We therefore saw a need for detection methods that could identify individuals suffering from S. aureus infections where α-hemolysin was a major determinant. Molecular imprinted polymers were subsequently prepared on gold coated sensor chips. Used in combination with a surface plasmon resonance biosensor, α-hemolysin could therethrough be quantified from septic blood samples (n = 9), without pre-culturing of the infectious agent. The biosensor recognized α-hemolysin with high affinity (KD = 2.75 x 10-7 M) and demonstrated a statistically significant difference (p < 0.0001) between the α-hemolysin response and potential sample contaminants. The detection scheme proved equally good, or better, when compared to antibody-based detection methods. This novel detection scheme constitutes a more rapid, economical, and user-friendly alternative to many methods currently in use. Heightening both reproducibility and sensitivity, molecular imprinting in combination with surface plasmon resonance (SPR)-technology could be a versatile new tool in clinical- and research-settings alike.
|
|
| 8. |
- Armbruster, Chelsie E., et al.
(författare)
-
Editorial : Rising stars in biofilms 2022
- 2023
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 13
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 9. |
|
|
| 10. |
- Bahrami, F., et al.
(författare)
-
Biomarkers of Cutaneous Leishmaniasis
- 2018
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Cutaneous leishmaniasis (CL) is an immune-mediated skin pathology caused mainly by Leishmania (L.) major, Leishmania tropica, Leishmania braziliensis, L. mexicana, and L. arnazonensis. The burden of CL in terms of morbidity and social stigmas are concentrated on certain developing countries in Asia, Africa, and South America. People with asymptomatic CL represent a large proportion of the infected individuals in the endemic areas who exhibit no lesion and can control the infection by as yet not fully understood mechanisms. Currently, there is no approved prophylactic control measure for CL. Discovery of biomarkers of CL infection and immunity can inform the development of more precise diagnostics tools as well as curative or preventive strategies to control CL. Herein, we provide a brief overview of the state-of-the-art for the biomarkers of CL with a special emphasis on the asymptomatic CL biomarkers. Among the identified CL biomarkers so far, direct biomarkers which indicate the actual presence of the infection as well as indirect biomarkers which reflect the host's reaction to the infection, such as alterations in delayed type hypersensitivity, T-cell subpopulations and cytokines, adenosine deaminase, and antibodies against the sand fly saliva proteins are discussed in detail. The future avenues such as the use of systems analysis to identify and characterize novel CL biomarkers are also discussed.
|
|
| 11. |
- Bai, JW, et al.
(författare)
-
Isolation and Characterization of vB_kpnM_17-11, a Novel Phage Efficient Against Carbapenem-Resistant Klebsiella pneumoniae
- 2022
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12, s. 897531-
-
Tidskriftsartikel (refereegranskat)abstract
- Phages and phage-encoded proteins exhibit promising prospects in the treatment of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) infections. In this study, a novel Klebsiella pneumoniae phage vB_kpnM_17-11 was isolated and identified by using a CRKP host. vB_kpnM_17-11 has an icosahedral head and a retractable tail. The latent and exponential phases were 30 and 60 minutes, respectively; the burst size was 31.7 PFU/cell and the optimal MOI was 0.001. vB_kpnM_17-11 remained stable in a wide range of pH (4-8) and temperature (4-40°C). The genome of vB_kpnM_17-11 is 165,894 bp, double-stranded DNA (dsDNA), containing 275 Open Reading Frames (ORFs). It belongs to the family of Myoviridae, order Caudovirales, and has a close evolutionary relationship with Klebsiella phage PKO111. Sequence analysis showed that the 4530 bp orf022 of vB_kpnM_17-11 encodes a putative depolymerase. In vitro testing demonstrated that vB_kpnM_17-11 can decrease the number of K. pneumoniae by 105-fold. In a mouse model of infection, phage administration improved survival and reduced the number of K. pneumoniae in the abdominal cavity by 104-fold. In conclusion, vB_kpnM_17-11 showed excellent in vitro and in vivo performance against K. pneumoniae infection and constitutes a promising candidate for the development of phage therapy against CRKP.
|
|
| 12. |
|
|
| 13. |
- Bajrai, LH, et al.
(författare)
-
Gene Expression Profiling of Early Acute Febrile Stage of Dengue Infection and Its Comparative Analysis With Streptococcus pneumoniae Infection
- 2021
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 11, s. 707905-
-
Tidskriftsartikel (refereegranskat)abstract
- Infectious diseases are the disorders caused by organisms such as bacteria, viruses, fungi, or parasites. Although many of them are permentantly hazardous, a number of them live in and on our bodies and they are normally harmless or even helpful. Under certain circumstances, some organisms may cause diseases and these infectious diseases may be passed directly from person to person or via intermediate vectors including insects and other animals. Dengue virus and Streptococcus pneumoniae are the critical and common sources of infectious diseases. So, it is critical to understand the gene expression profiling and their inferred functions in comparison to the normal and virus infected conditions. Here, we have analyzed the gene expression profiling for dengue hemorrhagic fever, dengue fever, and normal human dataset. Similar to it, streptococcus pneumoniae infectious data were analyzed and both the outcomes were compared. Our study leads to the conclusion that the dengue hemorrhagic fever arises in result to potential change in the gene expression pattern, and the inferred functions obviously belong to the immune system, but also there are some additional potential pathways which are critical signaling pathways. In the case of pneumoniae infection, 19 pathways were enriched, almost all these pathways are associated with the immune system and 17 of the enriched pathways were common with dengue infection except platelet activation and antigen processing and presentation. In terms of the comparative study between dengue virus and Streptococcus pneumoniae infection, we conclude that cell adhesion molecules (CAMs), MAPK signaling pathway, natural killer cell mediated cytotoxicity, regulation of actin cytoskeleton, and cytokine-cytokine receptor interaction are commonly enriched in all the three cases of dengue infection and Streptococcus pneumoniae infection, focal adhesion was enriched between classical dengue fever — dengue hemorrhagic fever, dengue hemorrhagic fever—normal samples, and SP, and antigen processing and presentation and Leukocyte transendothelial migration were enriched in classical dengue fever —normal samples, dengue hemorrhagic fever—normal samples, and Streptococcus pneumoniae infection.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Bashir, Zahra, et al.
(författare)
-
Investigations of microbiota composition and neuroactive pathways in association with symptoms of stress and depression in a cohort of healthy women
- 2024
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Despite mounting evidence of gut-brain involvement in psychiatric conditions, functional data remain limited, and analyses of other microbial niches, such as the vaginal microbiota, are lacking in relation to mental health. This aim of this study was to investigate if the connections between the gut microbiome and mental health observed in populations with a clinical diagnosis of mental illness extend to healthy women experiencing stress and depressive symptoms. Additionally, this study examined the functional pathways of the gut microbiota according to the levels of psychological symptoms. Furthermore, the study aimed to explore potential correlations between the vaginal microbiome and mental health parameters in young women without psychiatric diagnoses.Methods: In this cross-sectional study, 160 healthy Danish women (aged 18-40 years) filled out questionnaires with validated scales measuring symptoms of stress and depression and frequency of dietary intake. Fecal and vaginal microbiota samples were collected at the beginning of the menstrual cycle and vaginal samples were also collected at cycle day 8-12 and 18-22. Shotgun metagenomic profiling of the gut and vaginal microbiome was performed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for functional profiling and 56 Gut Brain Modules were analyzed in the fecal samples.Results: The relative abundance in the gut of the genera Escherichia, Parabacteroides, and Shigella was higher in women with elevated depressive symptoms. Women with high perceived stress showed a tendency of increased abundance of Escherichia, Shigella, and Blautia. Amongst others, the potentially pathogenic genera, Escherichia and Shigella correlate with alterations in the neuroactive pathways such as the glutamatergic, GABAeric, dopaminergic, and Kynurenine pathways. Vaginosis symptoms were more prevalent in women reporting high levels of stress and depressive symptoms.Conclusions: The findings of this study support the concept of a microbiota-associated effect on the neuroactive pathways even in healthy young women. This suggest, that targeting the gut microbiome could be a promising approach for future psychiatric interventions.
|
|
| 17. |
- Bhandage, Amol, 1988-, et al.
(författare)
-
Calling in the CaValry-Toxoplasma gondii Hijacks GABAergic Signaling and Voltage-Dependent Calcium Channel Signaling for Trojan horse-Mediated Dissemination
- 2019
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Dendritic cells (DCs) are regarded as the gatekeepers of the immune system but can also mediate systemic dissemination of the obligate intracellular parasite Toxoplasma gondii. Here, we review the current knowledge on how T. gondii hijacks the migratory machinery of DCs and microglia. Shortly after active invasion by the parasite, infected cells synthesize and secrete the neurotransmitter γ-aminobutyric acid (GABA) and activate GABA-A receptors, which sets on a hypermigratory phenotype in parasitized DCs in vitro and in vivo. The signaling molecule calcium plays a central role for this migratory activation as signal transduction following GABAergic activation is mediated via the L-type voltage-dependent calcium channel (L-VDCC) subtype Cav1.3. These studies have revealed that DCs possess a GABA/L-VDCC/Cav1.3 motogenic signaling axis that triggers migratory activation upon T. gondii infection. Moreover, GABAergic migration can cooperate with chemotactic responses. Additionally, the parasite-derived protein Tg14-3-3 has been associated with hypermigration of DCs and microglia. We discuss the interference of T. gondii infection with host cell signaling pathways that regulate migration. Altogether, T. gondii hijacks non-canonical signaling pathways in infected immune cells to modulate their migratory properties, and thereby promote its own dissemination.
|
|
| 18. |
- Bhandage, Amol K., et al.
(författare)
-
Toxoplasma-Induced Hypermigration of Primary Cortical Microglia Implicates GABAergic Signaling
- 2019
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Toxoplasma gondii is a widespread obligate intracellular parasite that causes chronic infection and life-threatening acute infection in the central nervous system. Previous work identified Toxoplasma-infected microglia and astrocytes during reactivated infections in mice, indicating an implication of glial cells in acute toxoplasmic encephalitis. However, the mechanisms leading to the spread of Toxoplasma in the brain parenchyma remain unknown. Here, we report that, shortly after invasion by T. gondii tachyzoites, parasitized microglia, but not parasitized astrocytes, undergo rapid morphological changes and exhibit dramatically enhanced migration in 2-dimensional and 3-dimensional matrix confinements. Interestingly, primary microglia secreted the neurotransmitter gamma-aminobutyric acid (GABA) in the supernatant as a consequence of T. gondii infection but not upon stimulation with LPS or heat-inactivated T. gondii. Further, microglia transcriptionally expressed components of the GABAergic machinery, including GABA-A receptor subunits, regulatory molecules and voltage-dependent calcium channels (VDCCs). Further, their transcriptional expression was modulated by challenge with T. gondii. Transcriptional analysis indicated that GABA was synthesized via both, the conventional pathway (glutamate decarboxylases GAD65 and GAD67) and a more recently characterized alternative pathway (aldehyde dehydrogenases ALDH2 and ALDH1a1). Pharmacological inhibitors targeting GABA synthesis, GABA-A receptors, GABA-A regulators and VDCC signaling inhibited Toxoplasma-induced hypermotility of microglia. Altogether, we show that primary microglia express a GABAergic machinery and that T. gondii induces hypermigration of microglia in a GABA-dependent fashion. We hypothesize that migratory activation of parasitized microglia by Toxoplasma may promote parasite dissemination in the brain parenchyma.
|
|
| 19. |
- Bobcakova, Anna, et al.
(författare)
-
Immune Profile in Patients With COVID-19 : Lymphocytes Exhaustion Markers in Relationship to Clinical Outcome
- 2021
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The velocity of the COVID-19 pandemic spread and the variable severity of the disease course has forced scientists to search for potential predictors of the disease outcome. We examined various immune parameters including the markers of immune cells exhaustion and activation in 21 patients with COVID-19 disease hospitalised in our hospital during the first wave of the COVID-19 pandemic in Slovakia. The results showed significant progressive lymphopenia and depletion of lymphocyte subsets (CD3+, CD4+, CD8+ and CD19+) in correlation to the disease severity. Clinical recovery was associated with significant increase in CD3+ and CD3+CD4+ T-cells. Most of our patients had eosinopenia on admission, although no significant differences were seen among groups with different disease severity. Non-survivors, when compared to survivors, had significantly increased expression of PD-1 on CD4+ and CD8+ cells, but no significant difference in Tim-3 expression was observed, what suggests possible reversibility of immune paralysis in the most severe group of patients. During recovery, the expression of Tim-3 on both CD3+CD4+ and CD3+CD8+ cells significantly decreased. Moreover, patients with fatal outcome had significantly higher proportion of CD38+CD8+ cells and lower proportion of CD38+HLA-DR+CD8+ cells on admission. Clinical recovery was associated with significant decrease of proportion of CD38+CD8+ cells. The highest AUC values within univariate and multivariate logistic regression were achieved for expression of CD38 on CD8+ cells and expression of PD1 on CD4+ cells alone or combined, what suggests, that these parameters could be used as potential biomarkers of poor outcome. The assessment of immune markers could help in predicting outcome and disease severity in COVID-19 patients. Our observations suggest, that apart from the degree of depletion of total lymphocytes and lymphocytes subsets, increased expression of CD38 on CD3+CD8+ cells alone or combined with increased expression of PD-1 on CD3+CD4+ cells, should be regarded as a risk factor of an unfavourable outcome in COVID-19 patients. Increased expression of PD-1 in the absence of an increased expression of Tim-3 on CD3+CD4+ and CD3+CD8+ cells suggests potential reversibility of ongoing immune paralysis in patients with the most severe course of COVID-19.
|
|
| 20. |
- Bostanci, Nagihan, et al.
(författare)
-
Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar.
- 2021
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera Campylobacter, Haemophilus, Prevotella, and Oribacterium varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that Prevotella and Veillonella were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.
|
|
| 21. |
- Bourgard, Catarina, 1985, et al.
(författare)
-
Plasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and Proteomics.
- 2018
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 8
-
Forskningsöversikt (refereegranskat)abstract
- During the last decade, the vast omics field has revolutionized biological research, especially the genomics, transcriptomics and proteomics branches, as technological tools become available to the field researcher and allow difficult question-driven studies to be addressed. Parasitology has greatly benefited from next generation sequencing (NGS) projects, which have resulted in a broadened comprehension of basic parasite molecular biology, ecology and epidemiology. Malariology is one example where application of this technology has greatly contributed to a better understanding ofPlasmodiumspp. biology and host-parasite interactions. Among the several parasite species that cause human malaria, the neglected Plasmodium vivax presents great research challenges, asin vitroculturing is not yet feasible and functional assays are heavily limited. Therefore, there are gaps in our P. vivax biology knowledge that affect decisions for control policies aiming to eradicate vivax malaria in the near future. In this review, we provide a snapshot of key discoveries already achieved in P. vivax sequencing projects, focusing on developments, hurdles, and limitations currently faced by the research community, as well as perspectives on future vivax malaria research.
|
|
| 22. |
- Brokaw, A., et al.
(författare)
-
Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy
- 2021
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.
|
|
| 23. |
- Bronnec, Vicky, et al.
(författare)
-
Propionibacterium (Cutibacterium) granulosum Extracellular DNase BmdE Targeting Propionibacterium (Cutibacterium) acnes Biofilm Matrix, a Novel Inter-Species Competition Mechanism
- 2022
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Acne vulgaris is the most common dermatological disorder worldwide affecting more than 80% of adolescents and young adults with a global prevalence of 231 million cases in 2019. The involvement of the skin microbiome disbalance in the pathophysiology of acne is recognized, especially regarding the relative abundance and diversity of Propionibacterium acnes a well-known dominant human skin commensal. Biofilms, where bacteria are embedded into a protective polymeric extracellular matrix, are the most prevalent life style for microorganisms. P. acnes and its biofilm-forming ability is believed to be a contributing factor in the development of acne vulgaris, the persistence of the opportunistic pathogen and antibiotic therapy failures. Degradation of the extracellular matrix is one of the strategies used by bacteria to disperse the biofilm of competitors. In this study, we report the identification of an endogenous extracellular nuclease, BmdE, secreted by Propionibacterium granulosum able to degrade P. acnes biofilm both in vivo and in vitro. This, to our knowledge, may represent a novel competitive mechanism between two closely related species in the skin. Antibiotics targeting P. acnes have been the mainstay in acne treatment. Extensive and long-term use of antibiotics has led to the selection and spread of resistant bacteria. The extracellular DNase BmdE may represent a new bio-therapeutical strategy to combat P. acnes biofilm in acne vulgaris.
|
|
| 24. |
- Chahal, Gurdeep, et al.
(författare)
-
Streptococcus oralis Employs Multiple Mechanisms of Salivary Mucin Binding That Differ Between Strains
- 2022
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus oralis is an oral commensal and opportunistic pathogen that can enter the bloodstream and cause bacteremia and infective endocarditis. Here, we investigated the mechanisms of S. oralis binding to oral mucins using clinical isolates, isogenic mutants and glycoconjugates. S. oralis bound to both MUC5B and MUC7, with a higher level of binding to MUC7. Mass spectrometry identified 128 glycans on MUC5B, MUC7 and the salivary agglutinin (SAG). MUC7/SAG contained a higher relative abundance of Lewis type structures, including Lewis b/y, sialyl-Lewis a/x and alpha 2,3-linked sialic acid, compared to MUC5B. S. oralis subsp. oralis binding to MUC5B and MUC7/SAG was inhibited by Lewis b and Lacto-N-tetraose glycoconjugates. In addition, S. oralis binding to MUC7/SAG was inhibited by sialyl Lewis x. Binding was not inhibited by Lacto-N-fucopentaose, H type 2 and Lewis x conjugates. These data suggest that three distinct carbohydrate binding specificities are involved in S. oralis subsp. oralis binding to oral mucins and that the mechanisms of binding MUC5B and MUC7 differ. Efficient binding of S. oralis subsp. oralis to MUC5B and MUC7 required the gene encoding sortase A, suggesting that the adhesin(s) are LPXTG-containing surface protein(s). Further investigation demonstrated that one of these adhesins is the sialic acid binding protein AsaA.
|
|
| 25. |
- Chao, Yashuan, et al.
(författare)
-
Biofilm-dispersed pneumococci induce elevated leukocyte and platelet activation
- 2024
-
Ingår i: Frontiers in cellular and infection microbiology. - 2235-2988. ; 14, s. 1-14
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Streptococcus pneumoniae (the pneumococcus) effectively colonizes the human nasopharynx, but can migrate to other host sites, causing infections such as pneumonia and sepsis. Previous studies indicate that pneumococci grown as biofilms have phenotypes of bacteria associated with colonization whereas bacteria released from biofilms in response to changes in the local environment (i.e., dispersed bacteria) represent populations with phenotypes associated with disease. How these niche-adapted populations interact with immune cells upon reaching the vascular compartment has not previously been studied. Here, we investigated neutrophil, monocyte, and platelet activation using ex vivo stimulation of whole blood and platelet-rich plasma with pneumococcal populations representing distinct stages of the infectious process (biofilm bacteria and dispersed bacteria) as well as conventional broth-grown culture (planktonic bacteria). METHODS: Flow cytometry and ELISA were used to assess surface and soluble activation markers for neutrophil and monocyte activation, platelet-neutrophil complex and platelet-monocyte complex formation, and platelet activation and responsiveness.RESULTS: Overall, we found that biofilm-derived bacteria (biofilm bacteria and dispersed bacteria) induced significant activation of neutrophils, monocytes, and platelets. In contrast, little to no activation was induced by planktonic bacteria. Platelets remained functional after stimulation with bacterial populations and the degree of responsiveness was inversely related to initial activation. Bacterial association with immune cells followed a similar pattern as activation.DISCUSSION: Differences in activation of and association with immune cells by biofilm-derived populations could be an important consideration for other pathogens that have a biofilm state. Gaining insight into how these bacterial populations interact with the host immune response may reveal immunomodulatory targets to interfere with disease development.
|
|
| 26. |
- Chao, Yashuan, et al.
(författare)
-
Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease.
- 2015
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae (the pneumococcus) is a common colonizer of the human nasopharynx. Despite a low rate of invasive disease, the high prevalence of colonization results in millions of infections and over one million deaths per year, mostly in individuals under the age of 5 and the elderly. Colonizing pneumococci form well-organized biofilm communities in the nasopharyngeal environment, but the specific role of biofilms and their interaction with the host during colonization and disease is not yet clear. Pneumococci in biofilms are highly resistant to antimicrobial agents and this phenotype can be recapitulated when pneumococci are grown on respiratory epithelial cells under conditions found in the nasopharyngeal environment. Pneumococcal biofilms display lower levels of virulence in vivo and provide an optimal environment for increased genetic exchange both in vitro and in vivo, with increased natural transformation seen during co-colonization with multiple strains. Biofilms have also been detected on mucosal surfaces during pneumonia and middle ear infection, although the role of these biofilms in the disease process is debated. Recent studies have shown that changes in the nasopharyngeal environment caused by concomitant virus infection, changes in the microflora, inflammation, or other host assaults trigger active release of pneumococci from biofilms. These dispersed bacteria have distinct phenotypic properties and transcriptional profiles different from both biofilm and broth-grown, planktonic bacteria, resulting in a significantly increased virulence in vivo. In this review we discuss the properties of pneumococcal biofilms, the role of biofilm formation during pneumococcal colonization, including their propensity for increased ability to exchange genetic material, as well as mechanisms involved in transition from asymptomatic biofilm colonization to dissemination and disease of otherwise sterile sites. Greater understanding of pneumococcal biofilm formation and dispersion will elucidate novel avenues to interfere with the spread of antibiotic resistance and vaccine escape, as well as novel strategies to target the mechanisms involved in induction of pneumococcal disease.
|
|
| 27. |
- Chen, Shiyun, et al.
(författare)
-
Environmental Regulation of Yersinia Pathophysiology
- 2016
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A. - 2235-2988. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Hallmarks of Yersinia pathogenesis include the ability to form biofilms on surfaces, the ability to establish close contact with eukaryotic target cells and the ability to hijack eukaryotic cell signaling and take over control of strategic cellular processes. Many of these virulence traits are already well-described. However, of equal importance is knowledge of both confined and global regulatory networks that collaborate together to dictate spatial and temporal control of virulence gene expression. This review has the purpose to incorporate historical observations with new discoveries to provide molecular insight into how some of these regulatory mechanisms respond rapidly to environmental flux to govern tight control of virulence gene expression by pathogenic Yersinia.
|
|
| 28. |
- Claesson, Rolf, et al.
(författare)
-
Multilocus Sequence Typing of Non-JP2 Serotype b Aggregatibacter actinomycetemcomitans Strains of Ghanaian and Swedish Origin
- 2021
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Objective and Methods: The Gram-negative bacterium, Aggregatibacter actinomycetemcomitans is associated with periodontitis affecting young individuals. The geographic dissemination of the highly leukotoxic JP2 genotype of serotype b of this species was previously studied by multilocus sequence typing (MLST). Here, we have used MLST to genetically characterize non-JP2 genotype strains of serotype b, isolated from individuals living in Ghana (n=41), and in Sweden (n=13), respectively.Results: The MLST analysis revealed a total of nine sequence types (ST). Both Ghanaian and Swedish isolates were distributed in ST 1-3. ST 5 and 6 were only identified among the Ghanaian strains, whereas ST 4, 7, 8 and 9 were uniquely represented among the Swedish strains. Previously, we characterized these non-JP2 genotype strains of A. actinomycetemcomitans serotype b by arbitrarily-primed (AP)-PCR, which distributed them into three groups, AP-PCR type 1, 2, and 3, respectively. AP-PCR type 1 strains are generally highly leukotoxic, and are associated with progression of periodontal attachment loss. As AP-PCR type 1 includes both JP2 genotype strains and a proportion of non-JP2 genotype strains of serotype b, a straightforward diagnostic procedure has been sought. This has revealed a gene, cagE, which appears to be conserved only in this AP-PCR type. According to our results, MLST was not a highly discriminatory method to identify AP-PCR type 1, as strains of this AP-PCR type could be found within three different ST: ST 2, ST 3 and ST 8.Conclusion: According to MLST, a geographic dissemination of non-JP2 genotype A. actinomycetemcomitans serotype b appears to exist. However, aiming to identify carriers of AP-PCR type 1, non-JP2 genotype serotype b, PCR with cagE-specific primers is likely the most efficient diagnostic procedure known today.
|
|
| 29. |
- Curtis, Michael W., et al.
(författare)
-
Identification of amino acid domains of Borrelia burgdorferi P66 that are surface exposed and important for localization, oligomerization, and porin function of the protein
- 2022
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- P66, a bifunctional integral outer membrane protein, is necessary for Borrelia burgdorferi to establish initial infection and to disseminate in mice. The integrin binding function of P66 facilitates extravasation and dissemination, but the role of its porin function during murine infection has not been investigated. A limitation to studying P66 porin function during mammalian infection has been the lack of structural information for P66. In this study, we experimentally characterized specific domains of P66 with regard to structure and function. First, we aligned the amino acid sequences of P66 from Lyme disease-causing Borrelia and relapsing fever-causing Borrelia to identify conserved and unique domains between these disease-causing clades. Then, we examined whether specific domains of P66 are exposed on the surface of the bacteria by introducing c-Myc epitope tags into each domain of interest. The c-Myc epitope tag inserted C-terminally to E33 (highly conserved domain), to T187 (integrin binding region domain and a non-conserved domain), and to E334 (non-conserved domain) were all detected on the surface of Borrelia burgdorferi. The c-Myc epitope tag inserted C-terminally to E33 and D303 in conserved domains disrupted P66 oligomerization and porin function. In a murine model of infection, the E33 and D303 mutants exhibited decreased infectivity and dissemination. Taken together, these results suggest the importance of these conserved domains, and potentially P66 porin function, in vivo.
|
|
| 30. |
|
|
| 31. |
- Dahlstrand Rudin, Agnes, et al.
(författare)
-
Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids
- 2021
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such as Porphyromonas gingivalis. The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growing P. gingivalis, and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found in P. gingivalis supernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed by P. gingivalis (and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context of P. gingivalis colonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.
|
|
| 32. |
- Darvish Alipoor, Shamila, et al.
(författare)
-
Significance of extracellular vesicles in orchestration of immune responses in Mycobacterium tuberculosis infection
- 2024
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : FRONTIERS MEDIA SA. - 2235-2988. ; 14
-
Forskningsöversikt (refereegranskat)abstract
- Mycobacterium tuberculosis (M.tb), the causative agent of Tuberculosis, is an intracellular bacterium well known for its ability to subvert host energy and metabolic pathways to maintain its intracellular survival. For this purpose, the bacteria utilize various mechanisms of which extracellular vehicles (EVs) related mechanisms attracted more attention. EVs are nanosized particles that are released by almost all cell types containing active biomolecules from the cell of origin and can target bioactive pathways in the recipient cells upon uptake. It is hypothesized that M.tb dictates the processes of host EV biogenesis pathways, selectively incorporating its molecules into the host EV to direct immune responses in its favor. During infection with Mtb, both mycobacteria and host cells release EVs. The composition of these EVs varies over time, influenced by the physiological and nutritional state of the host environment. Additionally, different EV populations contribute differently to the pathogenesis of disease at various stages of illness participating in a complex interplay between host cells and pathogens. These interactions ultimately influence immune responses and disease outcomes. However, the precise mechanisms and roles of EVs in pathogenicity and disease outcomes remain to be fully elucidated. In this review, we explored the properties and function of EVs in the context of M.tb infection within the host microenvironment and discussed their capacity as a novel therapeutic strategy to combat tuberculosis.
|
|
| 33. |
- Davies, Emma, et al.
(författare)
-
Genomic and Phenotypic Characterisation of Campylobacter jejuni Isolates From a Waterborne Outbreak
- 2020
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : FRONTIERS MEDIA SA. - 2235-2988. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Campylobacter infections are the leading cause of bacterial gastroenteritis. In Europe, over 246,000 cases are confirmed annually. Infections are often transmitted via contaminated food, such as poultry products, but water may be the source of infection as well. The aim of this study was to characterise a selection of Campylobacter jejuni human isolates, together with a water isolate, from a waterborne outbreak in Norway in 2019, including human isolates from early, mid-, and late epidemic. The isolates were characterised with whole-genome sequencing, analysing the expression of putative virulence genes and demonstrating the pathogenic potential in an in vitro adhesion model using HT-29 cells. All isolates belonged to the multilocus sequence type 1701 and ST45 clonal complex. In the genomic analysis, the water isolate clustered somewhat separately from the human isolates. There was some variation between the human isolates, but the water isolate seemed to display the greatest pathogenic potential, demonstrated by the highest levels of virulence gene expression, adhesion to epithelial cells and IL-8 induction. These results suggest that the water isolate of the study has potential to cause human infections, and that some bacterial changes due to host or environmental adaptation, may occur during a waterborne Campylobacter epidemic. This is, to the best of our knowledge, the first study on C. jejuni isolates from a waterborne outbreak, including both human isolates and a water isolate, characterised with genomic and phenotypic approaches.
|
|
| 34. |
- de Klerk, Nele, et al.
(författare)
-
The Host Cell Transcription Factor EGR1 Is Induced by Bacteria through the EGFR-ERK1/2 Pathway
- 2017
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- The essential first step in bacterial colonization is adhesion to the host epithelial cells. The early host-responses post-bacterial adhesions are still poorly understood. Early growth response 1 (EGR1) is an early response transcriptional regulator that can be rapidly induced by various environmental stimuli. Several bacteria can induce EGR1 expression in host cells, but the involved bacterial characteristics and the underlying molecular mechanisms of this response are largely unknown. Here, we show that EGR1 can be induced in host epithelial cells by different species of bacteria independent of the adherence level, Gram-staining type and pathogenicity. However, bacterial viability and contact with host cells is necessary, indicating that an active interaction between bacteria and the host is important. Furthermore, the strongest response is observed in cells originating from the natural site of the infection, suggesting that the EGR1 induction is cell type specific. Finally, we show that EGFRERK1/2 and beta 1-integrin signaling are the main pathways used for bacteria-mediated EGR1 upregulation. In conclusion, the increase of EGR1 expression in epithelial cells is a common stress induced, cell type specific response upon host-bacteria interaction that is mediated by EGFRERK1/2 and beta 1-integrin signaling.
|
|
| 35. |
- Demirel, Isak, 1987-, et al.
(författare)
-
Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells
- 2018
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- The NLRP3 inflammasome and IL-1 beta release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coil (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1 beta release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not MG1655, induced an increased caspase-1 activity and IL-1 beta release from bladder epithelial cells. The increase was shown to be mediated by et-hemolysin activation of the NLRP3 inflammasome in an NE-kappa B-independent manner. The effect of-hemolysin on IL-1 beta release was biphasic, initially suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON variant of CFT073 inhibited caspase-1 activation and IL-1 beta release. In addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was significantly reduced compare to wild-type cells. The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and alpha-hemolysin can modulate the activity of the NLRP3 inflammasome.
|
|
| 36. |
- Du, Y, et al.
(författare)
-
Influence of Pre-treatment Saliva Microbial Diversity and Composition on Nasopharyngeal Carcinoma Prognosis
- 2022
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12, s. 831409-
-
Tidskriftsartikel (refereegranskat)abstract
- The human microbiome has been reported to mediate the response to anticancer therapies. However, research about the influence of the oral microbiome on nasopharyngeal carcinoma (NPC) survival is lacking. We aimed to explore the effect of oral microbiota on NPC prognosis.MethodsFour hundred eighty-two population-based NPC cases in southern China between 2010 and 2013 were followed for survival, and their saliva samples were profiled using 16s rRNA sequencing. We analyzed associations of the oral microbiome diversity with mortality from all causes and NPC.ResultsWithin- and between-community diversities of saliva were associated with mortality with an average of 5.29 years follow-up. Lower Faith’s phylogenetic diversity was related to higher all-cause mortality [adjusted hazard ratio (aHR), 1.52 (95% confidence interval (CI), 1.06–2.17)] and NPC-specific mortality [aHR, 1.57 (95% CI, 1.07–2.29)], compared with medium diversity, but higher phylogenetic diversity was not protective. The third principal coordinate (PC3) identified from principal coordinates analysis (PCoA) on Bray–Curtis distance was marginally associated with reduced all-cause mortality [aHR, 0.85 (95% CI, 0.73–1.00)], as was the first principal coordinate (PC1) from PCoA on weighted UniFrac [aHR, 0.86 (95% CI, 0.74–1.00)], but neither was associated with NPC-specific mortality. PC3 from robust principal components analysis was associated with lower all-cause and NPC-specific mortalities, with HRs of 0.72 (95% CI, 0.61–0.85) and 0.71 (95% CI, 0.60–0.85), respectively.ConclusionsOral microbiome may be an explanatory factor for NPC prognosis. Lower within-community diversity was associated with higher mortality, and certain measures of between-community diversity were related to mortality. Specifically, candidate bacteria were not related to mortality, suggesting that observed associations may be due to global patterns rather than particular pathogens.
|
|
| 37. |
- Duguet, Thomas B., et al.
(författare)
-
Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism
- 2020
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Among the fundamental biological processes affected by microRNAs, small regulators of gene expression, a potential role in host-parasite communication is intriguing. We compared the miRNA complement of extracellular vesicles released by the free-living nematode Caenorhabditis elegans in culture to that of other adult parasitic nematodes. Expecting convergent functional roles for secreted miRNAs due to the common parasitic lifestyle of the organisms under investigation, we performed a miRNA sequence analysis as well as target search and pathway enrichment for potential mRNA targets within host immune functions. We found that the parasite miRNA seed sequences were more often identical to those of C. elegans, rather than to those of their hosts. However, we observed that the nematode-secreted miRNA fractions shared more often seed sequences with host miRNAs than those that are not found in the extracellular environment. Development and proliferation of immune cells was predicted to be affected several-fold by nematode miRNA release. In addition, we identified the AGE-RAGE signaling as a convergent targeted pathway by species-specific miRNAs from several parasitic species. We propose a multi-species comparative approach to differentiate those miRNAs that may have critical functions in host modulation, from those that may not. With our simple analysis, we put forward a workflow to study traits of parasitism at the miRNA level. This work will find even more resonance and significance, as an increasing amount of parasite miRNA collections are expected to be produced in the future.
|
|
| 38. |
- Ekestubbe, Sofie, 1982-, et al.
(författare)
-
The amino-terminal part of the needle-tip translocator LcrV of Yersinia pseudotuberculosis is required for early targeting of YopH and in vivo virulence
- 2016
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Type III secretion systems (T3SS) are dedicated to targeting anti-host effector proteins into the cytosol of the host cell to promote bacterial infection. Delivery of the effectors requires three specific translocator proteins, of which the hydrophilic translocator, LcrV, is located at the tip of the T3SS needle and is believed to facilitate insertion of the two hydrophobic translocators into the host cell membrane. Here we used Yersinia as a model to study the role of LcrV in T3SS mediated intracellular effector targeting. Intriguingly, we identified N-terminal IcrV mutants that, similar to the wild-type protein, efficiently promoted expression, secretion and intracellular levels of Yop effectors, yet they were impaired in their ability to inhibit phagocytosis by J774 cells. In line with this, the YopH mediated dephosphorylation of Focal Adhesion Kinase early after infection was compromised when compared to the wild type strain. This suggests that the mutants are unable to promote efficient delivery of effectors to their molecular targets inside the host cell upon host cell contact. The significance of this was borne out by the fact that the mutants were highly attenuated for virulence in the systemic mouse infection model. Our study provides both novel and significant findings that establish a role for LcrV in early targeting of effectors in the host cell.
|
|
| 39. |
- Eneslätt, Kjell, et al.
(författare)
-
Vaccine-mediated mechanisms controlling replication of Francisella tularensis in human peripheral blood mononuclear cells using a co-culture system
- 2018
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immunity (CMI) is normally required for efficient protection against intracellular infections, however, identification of correlates is challenging and they are generally lacking. Francisella tularensis is a highly virulent, facultative intracellular bacterium and CMI is critically required for protection against the pathogen, but how this is effectuated in humans is poorly understood. To understand the protective mechanisms, we established an in vitro co-culture assay to identify how control of infection of F. tularensis is accomplished by human cells and hypothesized that the model will mimic in vivo immune mechanisms. Non-adherent peripheral blood mononuclear cells (PBMCs) were expanded with antigen and added to cultures with adherent PBMC infected with the human vaccine strain, LVS, or the highly virulent SCHU S4 strain. Intracellular numbers of F. tularensis was followed for 72 h and secreted and intracellular cytokines were analyzed. Addition of PBMC expanded from naïve individuals, i.e., those with no record of immunization to F. tularensis, generally resulted in little or no control of intracellular bacterial growth, whereas addition of PBMC from a majority of F. tularensis-immune individuals executed static and sometimes cidal effects on intracellular bacteria. Regardless of infecting strain, statistical differences between the two groups were significant, P < 0.05. Secretion of 11 cytokines was analyzed after 72 h of infection and significant differences with regard to secretion of IFN-γ, TNF, and MIP-1β was observed between immune and naïve individuals for LVS-infected cultures. Also, in LVS-infected cultures, CD4 T cells from vaccinees, but not CD8 T cells, showed significantly higher expression of IFN-γ, MIP-1β, TNF, and CD107a than cells from naïve individuals. The co-culture system appears to identify correlates of immunity that are relevant for the understanding of mechanisms of the protective host immunity to F. tularensis.
|
|
| 40. |
- Eriksson, Kaja, et al.
(författare)
-
Salivary Microbiota and Host-Inflammatory Responses in Periodontitis Affected Individuals With and Without Rheumatoid Arthritis
- 2022
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPeriodontitis and rheumatoid arthritis (RA) are two widespread chronic inflammatory diseases with a previously suggested association. The objective of the current study was to compare the oral microbial composition and host ' s inflammatory mediator profile of saliva samples obtained from subjects with periodontitis, with and without RA, as well as to predict biomarkers, of bacterial pathogens and/or inflammatory mediators, for classification of samples associated with periodontitis and RA. MethodsSalivary samples were obtained from 53 patients with periodontitis and RA and 48 non-RA with chronic periodontitis. The microbial composition was identified using 16S rRNA gene sequencing and compared across periodontitis patients with and without RA. Levels of inflammatory mediators were determined using a multiplex bead assay, compared between the groups and correlated to the microbial profile. The achieved data was analysed using PCoA, DESeq2 and two machine learning algorithms, OPLS-DA and sPLS-DA. ResultsDifferential abundance DESeq2 analyses showed that the four most highly enriched (log2 FC >20) amplicon sequence variants (ASVs) in the non-RA periodontitis group included Alloprevotella sp., Prevotella sp., Haemophilus sp., and Actinomyces sp. whereas Granulicatella sp., Veillonella sp., Megasphaera sp., and Fusobacterium nucleatum were the most highly enriched ASVs (log2 FC >20) in the RA group. OPLS-DA with log2 FC analyses demonstrated that the top ASVs with the highest importance included Vampirovibrio sp. having a positive correlation with non-RA group, and seven ASVs belonging to Sphingomonas insulae, Sphingobium sp., Novosphingobium aromaticivorans, Delftia acidovorans, Aquabacterium spp. and Sphingomonas echinoides with a positive correlation with RA group. Among the detected inflammatory mediators in saliva samples, TWEAK/TNFSF12, IL-35, IFN-alpha 2, pentraxin-3, gp130/sIL6Rb, sIL-6Ra, IL-19 and sTNF-R1 were found to be significantly increased in patients with periodontitis and RA compared to non-RA group with periodontitis. Moreover, correlations between ASVs and inflammatory mediators using sPLS-DA analysis revealed that TWEAK/TNFSF12, pentraxin-3 and IL-19 were positively correlated with the ASVs Sphingobium sp., Acidovorax delafieldii, Novosphingobium sp., and Aquabacterium sp. ConclusionOur results suggest that the combination of microbes and host inflammatory mediators could be more efficient to be used as a predictable biomarker associated with periodontitis and RA, as compared to microbes and inflammatory mediators alone.
|
|
| 41. |
- Fasanya, Adebimpe, et al.
(författare)
-
Anti-phosphatidylserine antibody levels are low in multigravid pregnant women in a malaria-endemic area in Nigeria, and do not correlate with anti-VAR2CSA antibodies
- 2023
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Anemia is a common malaria-associated complication in pregnant women in endemic regions. Phosphatidylserine (PS) is exposed to the immune system during the massive destruction of red blood cells (RBCs) that accompany malaria, and antibodies against PS have been linked to anemia through destruction of uninfected RBCs. We determined levels of anti-PS IgG antibodies in pregnant women in Ibadan, Nigeria and correlated them to parameters of importance in development of anemia and immunity. Anti-PS correlated inversely with Packed Cell Volume (PCV), indicating that the antibodies could contribute to anemia. There was no correlation with anti-VAR2CSA IgG, haptoglobin or parasitemia, indicating that the modulation of anti-PS response is multifactorial in nature. Anti-PS levels were lowest in multigravidae compared to both primigravidae and secundigravidae and correlated inversely with age. In conclusion, lower levels of anti-PS in multigravidae could be beneficial in avoiding anemia.
|
|
| 42. |
- Fei, Ying, et al.
(författare)
-
Commensal Bacteria Augment Staphylococcus aureus septic Arthritis in a Dose-Dependent Manner.
- 2022
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis is considered one of the most dangerous joints diseases and is mainly caused by the Gram-positive bacterium Staphylococcus aureus (S. aureus). Human skin commensals are known to augment S. aureus infections. The aim of this study was to investigate if human commensals could augment S. aureus-induced septic arthritis.NMRI mice were inoculated with S. aureus alone or with a mixture of S. aureus together with either of the human commensal Staphylococcus epidermidis (S. epidermidis) or Streptococcus mitis (S. mitis). The clinical, radiological and histopathological changes due to septic arthritis were observed. Furthermore, the serum levels of chemokines and cytokines were assessed.Mice inoculated with a mixture of S. aureus and S. epidermidis or S. mitis developed more severe and frequent clinical arthritis compared to mice inoculated with S. aureus alone. This finding was verified pathologically and radiologically. Furthermore, the ability of mice to clear invading bacteria in the joints but not in kidneys was hampered by the bacterial mixture compared to S. aureus alone. Serum levels of monocyte chemoattractant protein 1 were elevated at the early phase of disease in the mice infected with bacterial mixture compared with ones infected with S. aureus alone. Finally, the augmentation effect in septic arthritis development by S. epidermidis was bacterial dose-dependent.The commensal bacteria dose-dependently augment S. aureus-induced septic arthritis in a mouse model of septic arthritis.
|
|
| 43. |
- Fernández-Santoscoy, Maria, et al.
(författare)
-
The Gut Microbiota Reduces Colonization of the Mesenteric Lymph Nodes and IL-12-Independent IFN-gamma Production During Salmonella Infection
- 2015
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- The intestinal commensal microbiota is essential for many host physiological processes, but its impact on infectious diseases is poorly understood. Here we investigate the influence of the gut microbiota during oral Salmonella infection. We report a higher bacterial burden in mesenteric lymph nodes (MLN) of intragastrically infected germ-free (GF) mice compared to conventionally-raised (CONV-R) animals, despite similar inflammatory phagocyte recruitment. Salmonella penetration into the lamina propria of the small intestine and splenic bacterial burden were not altered in the absence of the microbiota. Intragastrically infected GF mice also displayed a higher frequency of IFN-gamma-producing NK, NKT, CD4(+), and CD8(+) T cells in the MLN despite IL-12 levels similar to infected CONV-R mice. However, infecting mice intraperitoneally abrogated the difference in MLN bacterial load and IFN-gamma-producing cells observed in intragastrically-infected animals. Moreover, mice treated with antibiotics (ABX) and intragastrically infected with Salmonella had a greater bacterial burden and frequency of IFN-gamma-producing cells in the MLN. In ABX mice the number of Salmonella correlated with the frequency of IFN-gamma-producing lymphocytes in the MLN, while no such correlation was observed in the MLN of infected GF mice. Overall, the data show that the lack of the microbiota influences pathogen colonization of the MLN, and the increased IFN-gamma in the MLN of infected GF mice is not only due to the absence of commensals at the time of infection but the lack of immune signals provided by the microbiota from birth.
|
|
| 44. |
- Fish, Abigail I., et al.
(författare)
-
The Rickettsia conorii Adr1 interacts with the c-terminus of human vitronectin in a salt-sensitive manner
- 2017
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Spotted fever group (SFG) Rickettsia species are inoculated into the mammalian bloodstream by hematophagous arthropods. Once in the bloodstream and during dissemination, the survival of these pathogens is dependent upon the ability of these bacteria to evade serum-borne host defenses until a proper cellular host is reached. Rickettsia conorii expresses an outer membrane protein, Adr1, which binds the complement inhibitory protein vitronectin to promote resistance to the anti-bacterial effects of the terminal complement complex. Adr1 is predicted to consist of 8 transmembrane beta sheets that form a membrane-spanning barrel with 4 peptide loops exposed to the extracellular environment. We previously demonstrated that Adr1 derivatives containing either loop 3 or 4 are sufficient to bind Vn and mediate resistance to serum killing when expressed at the outer-membrane of E. coli. By expressing R. conorii Adr1 on the surface of non-pathogenic E. coli, we demonstrate that the interaction between Adr1 and vitronectin is salt-sensitive and cannot be interrupted by addition of heparin. Additionally, we utilized vitroenctin-derived peptides to map the minimal Adr1/vitronectin interaction to the C-terminal region of vitronectin. Furthermore, we demonstrate that specific charged amino acid residues located within loops 3 and 4 of Adr1 are critical for mediating resistance to complement-mediated killing. Interestingly, Adr1 mutants that were no longer sufficient to mediate resistance to serum killing still retained the ability to bind to Vn, suggesting that Adr1-Vn interactions responsible for resistance to serum killing are more complex than originally hypothesized. In summary, elucidation of the mechanisms governing Adr1-Vn binding will be useful to specifically target this protein-protein interaction for therapeutic intervention.
|
|
| 45. |
- Francis, Matthew S, et al.
(författare)
-
Editorial: The Pathogenic Yersiniae–Advances in the Understanding of Physiology and Virulence, Second Edition
- 2019
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 9, s. 1-5
-
Tidskriftsartikel (refereegranskat)abstract
- Of the 18 known Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica are pathogenic to humans and animals and are widely characterized. The zoonotic obligate pathogen Y. pestis is the causal agent of plague, a systemic disease that is usually fatal if left untreated (Zietz and Dunkelberg, 2004; Zhou et al., 2006). Free-living Y. enterocolitica and Y. pseudotuberculosis are the agents of yersiniosis, a rarely systemic gastrointestinal disease (Galindo et al., 2011). The remaining species are mostly harmless to humans, although Y. ruckeri is an enteric fish pathogen affecting mainly salmonids, while a few others display toxicity toward insects (Sulakvelidze, 2000; Tobback et al., 2007; Fuchs et al., 2008; Chen et al., 2010). At the forefront of Yersinia research are studies of classical microbiology, pathogenesis, protein secretion, niche adaptation, and regulation of gene expression. In pursuit of these endeavors, new frontiers are being forged on waves of methodological and technological innovation. In this second edition of the special research topic on the pathogenic Yersiniae is a compilation of reviews and research articles that summarize current knowledge and future research directions in the Yersinia pathophysiology field.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Frostadottir, Drifa, et al.
(författare)
-
Legionella longbeachae wound infection : case report and review of reported Legionella wound infections
- 2023
-
Ingår i: Frontiers in cellular and infection microbiology. - : FRONTIERS MEDIA SA. - 2235-2988. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Extrapulmonary manifestations of infection with Legionella species, of which 24 may cause disease in humans, are very rare. Here, we describe a case of a 61-year-old woman with no history of immunosuppression presenting with pain and swelling of her index finger after a prick by rose thorns during gardening. Clinical examination showed fusiform swelling of the finger with mild redness, warmth, and fever. The blood sample revealed a normal white blood cell count and a slight increase in C-reactive protein. Intraoperative observation showed extensive infectious destruction of the tendon sheath, while the flexor tendons were spared. Conventional cultures were negative, while 16S rRNA PCR analysis identified Legionella longbeachae that also could be isolated on buffered charcoal yeast extract media. The patient was treated with oral levofloxacin for 13 days, and the infection healed quickly. The present case report, with a review of the literature, indicates that Legionella species wound infections may be underdiagnosed due to the requirement for specific media and diagnostic methods. It emphasizes the need for heightened awareness of these infections during history taking and clinical examination of patients presenting with cutaneous infections.
|
|
| 49. |
- Gaballa, Ahmed, et al.
(författare)
-
More than mcr : canonical plasmid- and transposon-encoded mobilized colistin resistance genes represent a subset of phosphoethanolamine transferases
- 2023
-
Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Mobilized colistin resistance genes (mcr) may confer resistance to the last-resort antimicrobial colistin and can often be transmitted horizontally. mcr encode phosphoethanolamine transferases (PET), which are closely related to chromosomally encoded, intrinsic lipid modification PET (i-PET; e.g., EptA, EptB, CptA). To gain insight into the evolution of mcr within the context of i-PET, we identified 69,814 MCR-like proteins present across 256 bacterial genera (obtained by querying known MCR family representatives against the National Center for Biotechnology Information [NCBI] non-redundant protein database via protein BLAST). We subsequently identified 125 putative novel mcr-like genes, which were located on the same contig as (i) ≥1 plasmid replicon and (ii) ≥1 additional antimicrobial resistance gene (obtained by querying the PlasmidFinder database and NCBI’s National Database of Antibiotic Resistant Organisms, respectively, via nucleotide BLAST). At 80% amino acid identity, these putative novel MCR-like proteins formed 13 clusters, five of which represented putative novel MCR families. Sequence similarity and a maximum likelihood phylogeny of mcr, putative novel mcr-like, and ipet genes indicated that sequence similarity was insufficient to discriminate mcr from ipet genes. A mixed-effect model of evolution (MEME) indicated that site- and branch-specific positive selection played a role in the evolution of alleles within the mcr-2 and mcr-9 families. MEME suggested that positive selection played a role in the diversification of several residues in structurally important regions, including (i) a bridging region that connects the membrane-bound and catalytic periplasmic domains, and (ii) a periplasmic loop juxtaposing the substrate entry tunnel. Moreover, eptA and mcr were localized within different genomic contexts. Canonical eptA genes were typically chromosomally encoded in an operon with a two-component regulatory system or adjacent to a TetR-type regulator. Conversely, mcr were represented by single-gene operons or adjacent to pap2 and dgkA, which encode a PAP2 family lipid A phosphatase and diacylglycerol kinase, respectively. Our data suggest that eptA can give rise to “colistin resistance genes” through various mechanisms, including mobilization, selection, and diversification of genomic context and regulatory pathways. These mechanisms likely altered gene expression levels and enzyme activity, allowing bona fide eptA to evolve to function in colistin resistance.
|
|
| 50. |
- Gerner, Erik, 1986, et al.
(författare)
-
Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo.
- 2023
-
Ingår i: Frontiers in cellular and infection microbiology. - 2235-2988. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. Pseudomonas aeruginosa is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response.This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response.In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology.In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1β, IL-6, and IL-1α secretion, as compared with untreated supernatants.In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.
|
|
