| 1. |
- Mohanty, Soumitra, et al.
(författare)
-
Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder
- 2022
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity. Patients with diabetes have an increased susceptibility to infections. Here the authors show that high glucose impairs innate immunity through reduced levels of the antimicrobial peptide psoriasin and impaired epithelial barrier function, resulting in an increased risk of urinary tract infection.
|
|
| 2. |
- Mohanty, Soumitra, et al.
(författare)
-
Inhibition of COX-2 signaling favors E. coli during urinary tract infection
- 2023
-
Ingår i: Journal of Inflammation. - : BioMed Central (BMC). - 1476-9255. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To avoid the overuse of antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), acting via cyclooxygenase (COX) inhibition, have been used to reduce pain and as an alternative treatment for uncomplicated urinary tract infections (UTIs). However, clinical studies evaluating NSAIDs versus antibiotics have reported an increased risk of acute pyelonephritis. Therefore, we hypothesized that COX inhibition could compromise the innate immune response and contribute to complications in patients with uncomplicated UTI.Results: We here demonstrate that in particular COX-2 inhibition led to decreased expression of the antimicrobial peptides psoriasin and human β-defensin-2 in human uroepithelial cells. Psoriasin expression was altered in neutrophils and macrophages. COX-2 inhibition also had impact on the inflammasome mediated IL-1β expression in response to uroepithelial E. coli infection. Further, COX-2 inhibition downregulated free radicals and the epithelial barrier protein claudin 1, favoring infectivity. In addition, conditioned media from COX-2 inhibited uroepithelial cells infected with E. coli failed to activate macrophages.Conclusions: Taken together, our data suggests an adverse innate immune effect of COX-2 inhibition on uroepithelial cells during UTI.
|
|
| 3. |
- Brauner, Annelie, et al.
(författare)
-
Is there a risk of cancer development after Campylobacter infection?
- 2010
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 45:7-8, s. 893-897
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: All Campylobacter jejuni species produce a genotoxin, which induce DNA double strand breaks, could lead to an increased risk of cancer especially in the gastro-intestinal tract.MATERIAL AND METHODS: All individuals in Stockholm County who tested positive with C. jejuni between 1989 and 2006 were included. The cohort was followed-up until December 31, 2007 for the occurrence of cancer, overall and site specific. Standard incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparisons with the background population.RESULTS: There were 16,276 individuals who tested positive for C. jejuni generating 124,387 person years. Excluding the first year of follow-up the overall risk for cancer did neither differ from that expected SIR = 0.95 (95% CI 0.82-1.09) nor after 10 years or more of follow-up; SIR = 0.91 (95% CI 0.71-1.16). There was no increased risk for cancer in the gastro-intestinal tract, but there were significantly increased risks for melanomas SIR = 1.84 (95% CI 1.27-2.57) and squamous cell skin cancer SIR = 1.52 (95% CI 1.01-2.19) while a significantly decreased risk of respiratory cancers among males SIR = 0.32 (95% CI 0.12-0.70) was observed.CONCLUSIONS: Our results indicate no excess risks of malignancies following an infection by C. jejuni at least during the first decade. Furthermore, the finding of a decreased risk of respiratory cancers could be of interest, if the results are reproduced in future studies in other populations.
|
|
| 4. |
- Che, Karlhans Fru, et al.
(författare)
-
The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers
- 2018
-
Ingår i: Clinical Science. - 0143-5221. ; 132:9, s. 959-983
-
Tidskriftsartikel (refereegranskat)abstract
- Long-term tobacco smokers with chronic obstructive pulmonary disease (COPD) or chronic bronchitis display an excessive accumulation of neutrophils in the airways; an inflammation that responds poorly to established therapy. Thus, there is a need to identify new molecular targets for the development of effective therapy. Here, we hypothesized that the neutrophil-mobilizing cytokine interleukin (IL)-26 (IL-26) is involved in airway inflammation amongst long-term tobacco smokers with or without COPD, chronic bronchitis or colonization by pathogenic bacteria. By analyzing bronchoalveolar lavage (BAL), bronchail wash (BW) and induced sputum (IS) samples, we found increased extracellular IL-26 protein in the airways of long-term smokers in vivo without further increase amongst those with clinically stable COPD. In human alveolar macrophages (AM) in vitro, the exposure to water-soluble tobacco smoke components (WTC) enhanced IL-26 gene and protein. In this cell model, the same exposure increased gene expression of the IL-26 receptor complex (IL10R2 and IL20R1) and nuclear factor κ B (NF-κB); a proven regulator of IL-26 production. In the same cell model, recombinant human IL-26 in vitro caused a concentration-dependent increase in the gene expression of NF-κB and several pro-inflammatory cytokines. In the long-term smokers, we also observed that extracellular IL-26 protein in BAL samples correlates with measures of lung function, tobacco load, and several markers of neutrophil accumulation. Extracellular IL-26 was further increased in long-term smokers with exacerbations of COPD (IS samples), with chronic bronchitis (BAL samples ) or with colonization by pathogenic bacteria (IS and BW samples). Thus, IL-26 in the airways emerges as a promising target for improving the understanding of the pathogenic mechanisms behind several pulmonary morbidities in long-term tobacco smokers.
|
|
| 5. |
- Demirel, Isak, 1987-, et al.
(författare)
-
Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1β release and regulation of antimicrobial properties in human neutrophils
- 2020
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The NLRP3 inflammasome and IL-1β have recently been linked to the severity of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection (UTI). However, not much is known about the contribution of NLRP3 to the antimicrobial properties of neutrophils and the release of IL-1β during UPEC infection. The purpose of this study was to elucidate the mechanisms behind UPEC-induced IL-1β release from human neutrophils, and to investigate the contribution of the NLRP3 inflammasome in neutrophil-mediated inhibition of UPEC growth. We found that the UPEC strain CFT073 increased the expression of NLRP3 and increased caspase-1 activation and IL-1β release from human neutrophils. The IL-1β release was mediated by the NLRP3 inflammasome and by serine proteases in an NF-κB-and cathepsin B-dependent manner. The UPEC virulence factors α-hemolysin, type-1 fimbriae and p-fimbriae were all shown to contribute to UPEC mediated IL-1β release from neutrophils. Furthermore, inhibition of caspase-1 and NLRP3 activation increased neutrophil ROS-production, phagocytosis and the ability of neutrophils to suppress UPEC growth. In conclusion, this study demonstrates that UPEC can induce NLRP3 and serine protease-dependent release of IL-1β from human neutrophils and that NLRP3 and caspase-1 can regulate the antimicrobial activity of human neutrophils against UPEC.
|
|
| 6. |
- 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.
|
|
| 7. |
- El Mouali, Youssef, et al.
(författare)
-
Stand-alone EAL domain proteins form a distinct subclass of EAL proteins involved in regulation of cell motility and biofilm formation in enterobacteria
- 2017
-
Ingår i: Journal of Bacteriology. - : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 199:18
-
Tidskriftsartikel (refereegranskat)abstract
- The second messenger cyclic dimeric GMP (c-di-GMP) is almost ubiquitous among bacteria as are the c-di-GMP turnover proteins, which mediate the transition between motility and sessility. EAL domain proteins have been characterized as c-di-GMP-specific phosphodiesterases. While most EAL domain proteins contain additional, usually N-terminal, domains, there is a distinct family of proteins with stand-alone EAL domains, exemplified by Salmonella enterica serovar Typhimurium proteins STM3611 (YhjH/PdeH), a c-di-GMP-specific phosphodiesterase, and the enzymatically inactive STM1344 (YdiV/CdgR) and STM1697, which regulate bacterial motility through interaction with the flagellar master regulator, FlhDC. We have analyzed the phylogenetic distribution of EAL-only proteins and their potential functions. Genes encoding EAL-only proteins were found in various bacterial phyla, although most of them were seen in proteobacteria, particularly enterobacteria. Based on the conservation of the active site residues, nearly all stand-alone EAL domains encoded by genomes from phyla other than proteobacteria appear to represent functional phosphodiesterases. Within enterobacteria, EAL-only proteins were found to cluster either with YhjH or with one of the subfamilies of YdiV-related proteins. EAL-only proteins from Shigella flexneri, Klebsiella pneumoniae, and Yersinia enterocolitica were tested for their ability to regulate swimming and swarming motility and formation of the red, dry, and rough (rdar) biofilm morphotype. In these tests, YhjH-related proteins S4210, KPN_01159, KPN_03274, and YE4063 displayed properties typical of enzymatically active phosphodiesterases, whereas S1641 and YE1324 behaved like members of the YdiV/STM1697 subfamily, with Yersinia enterocolitica protein YE1324 shown to downregulate motility in its native host. Of two closely related EAL-only proteins, YE2225 is an active phosphodiesterase, while YE1324 appears to interact with FlhD. These results suggest that in FlhDC-harboring beta-and gammaproteobacteria, some EAL-only proteins evolved to become catalytically inactive and regulate motility and biofilm formation by interacting with FlhDC. IMPORTANCE The EAL domain superfamily consists mainly of proteins with cyclic dimeric GMP-specific phosphodiesterase activity, but individual domains have been classified in three classes according to their functions and conserved amino acid signatures. Proteins that consist solely of stand-alone EAL domains cannot rely on other domains to form catalytically active dimers, and most of them fall into one of two distinct classes: catalytically active phosphodiesterases with well-conserved residues of the active site and the dimerization loop, and catalytically inactive YdiV/CdgR-like proteins that regulate bacterial motility by binding to the flagellar master regulator, FlhDC, and are found primarily in enterobacteria. The presence of apparently inactive EAL-only proteins in the bacteria that do not express FlhD suggests the existence of additional EAL interaction partners.
|
|
| 8. |
- Fan, Yanmiao, et al.
(författare)
-
Dendritic Hydrogels Induce Immune Modulation in Human Keratinocytes and Effectively Eradicate Bacterial Pathogens
- 2021
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:41, s. 17180-17190
-
Tidskriftsartikel (refereegranskat)abstract
- Infections caused by antibiotic-resistant bacteria are globally a major threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers to protect people. Biomaterials that have inherent antibacterial properties and do not require the use of antibiotics present an attractive and feasible avenue to achieve this goal. Herein, we demonstrate the effect of a new class of cationic hydrogels based on amino-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) exhibiting excellent antimicrobial activity toward a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. Intriguingly, the hydrogels can induce the expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes (HaCaT). Moreover, treatment with the hydrogels decreased the proinflammatory cytokine IL-1 beta, reactive nitrogen species (NO), and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells, conjunctively resulting in reduced inflammation.
|
|
| 9. |
- Fan, Yanmiao, et al.
(författare)
-
Nanogel encapsulated hydrogels as advanced wound dressings for the controlled delivery of antibiotics
- 2021
-
Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 31
-
Tidskriftsartikel (refereegranskat)abstract
- Biocompatible and degradable dual-delivery gel systems based on hyperbrancheddendritic−linear−dendritic copolymers (HBDLDs) is herein conceptualizedand accomplished via thiol-ene click chemistry. The elasticity of thehydrogels is tunable by varying the lengths of PEG (2, 6, 10 kDa) or the dryweight percentages (20, 30, 40 wt%), and are found to be between 2–14.7 kPa,comparable to human skin. The co-delivery of antibiotics is achieved, wherethe hydrophilic drug novobiocin sodium salt (NB) is entrapped within thehydrophilic hydrogel, while the hydrophobic antibiotic ciprofloxacin (CIP) isencapsulated within the dendritic nanogels (DNGs) with hydrophobic cores(DNGs-CIP). The DNGs-CIP with drug loading capacity of 2.83 wt% are thenphysically entrapped within the hybrid hydrogels through UV curing. Thehybrid hydrogels enabled the quick release of NB and prolonged released ofCIP. In vitro cell infection assays showed that the antibiotic-loaded hybridhydrogels are able to treat bacterial infections with significant bacterialreduction. Hybrid hydrogel band aids are fabricated and exhibited betterantibacterial activity compared with commercial antimicrobial band aids.Remarkably, most hydrogels and hybrid hydrogels showed enhanced humandermal cell proliferation and could be degraded into non-toxic constituents,showing great promise as wound dressing materials.
|
|
| 10. |
- Fan, Yanmiao, et al.
(författare)
-
Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.
|
|
| 11. |
- Fan, Yanmiao
(författare)
-
The synthesis of dendritic hydrogels and inorganic nanoparticles and their application as antibacterial and imaging materials
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AbstractThe overuse and misuse of conventional antibiotics has caused increased prevalence of drug-resistant bacteria, the infections of which cause high mortality and economic losses per year. It is therefore crucial to develop new technologies and treatments for infections caused by drug-resistant bacteria. Dendritic polymer-based hydrogels and nanomaterials have shown promise as alternatives to traditional small-molecule antibiotics.Third generation (G3) allyl-functional hyperbranched dendritic-linear-dendritic copolymers (HBDLDs) based on polyethylene glycol (PEG) and 2,2-bis(hydroxymethyl) propionic acid (bis-MPA) were synthesized, and used to form hydrogels with a dithiol-functional PEG crosslinker using thiol-ene coupling (TEC). The hydrogels were used to co-deliver both hydrophilic and hydrophobic antibiotics with the aid of dendritic nanogels (DNGs). Antibacterial hydrogel band aids were also fabricated in a facile procedure.Amino-functional HBDLDs based on PEG and bis-MPA were synthesized, and together with a di-N-hydroxysuccinimide-functional PEG as the crosslinker, amino-functional hydrogels with inherent antibacterial properties were fabricated. The cationic hydrogels are highly effective towards a wide range of wound-isolated bacteria, and can reduce inflammation and oxidative stress.To minimize the cytotoxicity of amino-functional dendrimers, self-assembled hydrogels based on cationic dendrimers and cellulose nanofibrils were fabricated. Cationic dendrimers and their fragments can be released from the hydrogels to kill bacteria whilst showing insignificant cytotoxicity with human cells.Bis-MPA dendrimers with both amino and allyl functionalities were also synthesized. Allyl groups can be used to form hydrogels with a dithiol-functional PEG crosslinker via TEC, and the amino groups provide the hydrogels with antibacterial properties.Fluorescent silicon nanoparticles (SiNPs) were synthesized and their interaction with bacteria was investigated. SiNPs exhibited strong binding to Staphylococcus aureus (S. aureus), showing promise as a potential capturing and imaging agent for S. aureus.
|
|
| 12. |
- Hertting, Olof, et al.
(författare)
-
Vitamin D-deficient mice have more invasive urinary tract infection
- 2017
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 12:7
-
Tidskriftsartikel (refereegranskat)abstract
- Vitamin D deficiency is a common health problem with consequences not limited to bone and calcium hemostasis. Low levels have also been linked to tuberculosis and other respiratory infections as well as autoimmune diseases. We have previously shown that supplementation with vitamin D can induce the antimicrobial peptide cathelicidin during ex vivo infection of human urinary bladder. In rodents, however, cathelicidin expression is not linked to vitamin D and therefore this vitamin D-related effect fighting bacterial invasion is not relevant. To determine if vitamin D had further protective mechanisms during urinary tract infections, we therefore used a mouse model. In vitamin D-deficient mice, we detected more intracellular bacterial communities in the urinary bladder, higher degree of bacterial spread to the upper urinary tract and a skewed cytokine response. Furthermore, we show that the vitamin D receptor was upregulated in the urinary bladder and translocated into the cell nucleus after E. coli infection. This study supports a more general role for vitamin D as a local immune response mediator in the urinary tract.
|
|
| 13. |
- Kerr White, John, et al.
(författare)
-
A Synthetic Cyclized Antimicrobial Peptide with Potent Effects against Drug-Resistant Skin Pathogens
- 2023
-
Ingår i: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 9:5, s. 1056-1063
-
Tidskriftsartikel (refereegranskat)abstract
- Dermal infections requiring treatment are usually treated with conventional antibiotics, but the rise of bacterial resistance to first-line antibiotics warrants alternative therapeutics. Here, we report that a backbone-cyclized antimicrobial peptide, CD4-PP, designed from the human host defense peptide LL-37, has strong direct antibacterial effects on antibiotic sensitive as well as resistant-type strains and clinical isolates of common skin pathogens in the low (<2) μM range. In addition, it influences innate immunity in keratinocytes, and treatment with CD4-PP is able to clear bacterial infections in infected keratinocytes. Additionally, CD4-PP treatment significantly reduces the wound area in a lawn of keratinocytes infected with MRSA. In conclusion, CD4-PP has the potential to serve as a future drug treating wounds infected with antibiotic-resistant bacteria.
|
|
| 14. |
- Kihlström, Erik, 1948-, et al.
(författare)
-
Mykoplasma och Ureaplasma
- 2021. - 2
-
Ingår i: Medicinsk mikrobiologi & immunologi. - Lund : Studentlitteratur AB. - 9789144123578 ; , s. 325-328
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Ordet mykoplasma används ofta som trivialnamn när man avser arter inom klassen Mollicutes, vilka karakteriseras av att de till skillnad från andra bakterier saknar cellvägg. Namnen Mollicutes och Mykoplasma syftar på denna egenskap och betyder mjukt skinn respektive svampliknande och formbar. I dag finns över 200 Mollicutes beskrivna, de flesta patogenerna hittar man inom släktena Mycoplasma och Ureoplasma. Man har isolerat ett flertal mykoplasmaarter från människa och uppfyllt Kochs postulat för M. pneumoniae, M. hominis, M. genitalium och vissa Ureoplasma-arter. I detta kapitel kommer vi använda mykoplasma i en bredare bemärkelse när vi beskriver olika arter inom Mollicutes.
|
|
| 15. |
- Lewitt, Moira S., et al.
(författare)
-
Stereotyping at the undergraduate level revealed during interprofessional learning between future doctors and biomedical scientists
- 2010
-
Ingår i: Journal of Interprofessional Care. - : Informa UK Limited. - 1356-1820 .- 1469-9567. ; 24:1, s. 53-62
-
Tidskriftsartikel (refereegranskat)abstract
- Interprofessional education (IPE) involving undergraduate health professionals is expected to promote collaboration in their later careers. The role of IPE between doctors and biomedical scientists has not been explored at the undergraduate level. Our aim was to introduce IPE sessions for medical and biomedical students in order to identify the benefits and barriers to these groups learning together. Medical and biomedical students together discussed laboratory results, relevant literature, and ideas for developing new diagnostic tools. T]he programme was evaluated with questionnaires and interviews. While there was general support for the idea of IPE, medical and biomedical students responded differently. Biomedical students were more critical, wanted more explicit learning objectives and felt that their professional role was often misunderstood. The medical students were more enthusiastic but regarded the way the biomedical students communicated concerns about their perceived role as a barrier to effective interprofessional learning. We conclude that stereotyping, which can impede effective collaborations between doctors and biomedical scientists, is already present at the undergraduate level and may be a barrier to IPE. Effective learning opportunities should be supported at the curriculum level and be designed to specifically enable a broad appreciation of each other's future professional roles.
|
|
| 16. |
- Li, Fengyang, et al.
(författare)
-
Patatin-like phospholipase CapV in Escherichia coli-morphological and physiological effects of one amino acid substitution
- 2022
-
Ingår i: npj Biofilms and Microbiomes. - : Springer Science and Business Media LLC. - 2055-5008. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- In rod-shaped bacteria, morphological plasticity occurs in response to stress, which blocks cell division to promote filamentation. We demonstrate here that overexpression of the patatin-like phospholipase variant CapV(Q329R), but not CapV, causes pronounced sulA-independent pyridoxine-inhibited cell filamentation in the Escherichia coli K-12-derivative MG1655 associated with restriction of flagella production and swimming motility. Conserved amino acids in canonical patatin-like phospholipase A motifs, but not the nucleophilic serine, are required to mediate CapV(Q329R) phenotypes. Furthermore, CapV(Q329R) production substantially alters the lipidome and colony morphotype including rdar biofilm formation with modulation of the production of the biofilm activator CsgD, and affects additional bacterial traits such as the efficiency of phage infection and antimicrobial susceptibility. Moreover, genetically diverse commensal and pathogenic E. coli strains and Salmonella typhimurium responded with cell filamentation and modulation in colony morphotype formation to CapV(Q329R) expression. In conclusion, this work identifies the CapV variant CapV(Q329R) as a pleiotropic regulator, emphasizes a scaffold function for patatin-like phospholipases, and highlights the impact of the substitution of a single conserved amino acid for protein functionality and alteration of host physiology.
|
|
| 17. |
- Norinder, Birgit Stattin, et al.
(författare)
-
Do Escherichia coli strains causing acute cystitis have a distinct virulence repertoire?
- 2012
-
Ingår i: Microbial Pathogenesis. - : Elsevier BV. - 1096-1208 .- 0882-4010. ; 52:1, s. 10-16
-
Tidskriftsartikel (refereegranskat)abstract
- Bacterial virulence factors influence the site and severity of urinary tract infections. While pyelonephritis-associated molecular traits have been defined, virulence factors specific for acute cystitis strains have not been identified. This study examined the virulence factor repertoire of 247 Escherichia coli strains, prospectively isolated from women with community-acquired acute cystitis. Fim sequences were present in 96% of the isolates, which also expressed Type 1 fimbriae. Curli were detected in 75%, 13% of which formed cellulose. Pap sequences were present in 47%, 27% were papG+, 23% were prsG+ and 42% expressed P fimbriae. TcpC was expressed by 33% of the strains, 32% in a subgroup of patients who only had symptoms of cystitis and 42% in patients with signs of upper urinary tract involvement; most frequently by the papG+/prsG+ subgroup. Strains with the full fim, pap and TcpC and curli virulence profile were more common in cystitis patients with than in patients without upper tract involvement (p<0.05). The varied virulence profile of E. coli strains causing acute cystitis suggests that diverse bacterial strains, expressing Type 1 fimbriae trigger a convergent host response, involving pathways that give rise to the characteristic symptoms of acute cystitis.
|
|
| 18. |
- Sahlberg Bang, Charlotte, 1967-
(författare)
-
Carbon monoxide and nitric oxide as antimicrobial agents : focus on ESBL-producing uropathogenic E.coli
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Urinary tract infections (UTI) are common in humans and most often caused by uropathogenic Escherichia coli (E. coli). Extended-spectrum beta-lactamase (ESBL)-producing E. coli are increasing worldwide and they are frequently multidrug-resistant with limited treatment options. The overall aim of this thesis was to study the role of the host-derived factors nitric oxide (NO) and carbon monoxide (CO) as antimicrobial agents against ESBL-producing uropathogenic strains of E. coli (UPEC).The NO-donor DETA/NO caused a temporary growth inhibition in ESBL-producing UPEC. The antibacterial effect of DETA/NO was improved when DETA/NO was combined with miconazole, a pharmacological inhibitor of NO-protective mechanisms. Combination treatment with DETA/NO, miconazole and polymyxin B nonapeptid prolonged the bacteriostatic effect in the majority of examined isolates. The CO-donor CORM-2 showed a pronounced antibacterial effect in ESBL-producing UPEC with a fast bactericidal effect. Moreover, CORM-2 was shown to reduce the bacterial viability of ESBL-producing UPEC grown under biofilm-like conditions and to decrease the bacterial colonization of human bladder epithelial cells. A microarray analysis was performed to define transcriptomic targets of CORM-2 after a single exposure and after repeated exposure to CORM-2. Many processes were affected by CORM-2, including a downregulation in energy metabolism and biosynthesis pathways and upregulation of the SOS response and DNA repair. Repeated exposure to CORM-2 did not change the gene expression patterns or fold changes and the growth inhibitory response to CORM-2 was not altered after repeated exposure.In conclusion, NO- and CO-donors have antibacterial effects against ESBL-producing UPEC and may be interesting candidates for development of new antibiotics to treat UTI caused by multidrug-resistant uropathogens.
|
|
| 19. |
- Sennström, Maria B., et al.
(författare)
-
Human cervical ripening, an inflammatory process mediated by cytokines
- 2000
-
Ingår i: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1360-9947 .- 1460-2407. ; 6:4, s. 81-375
-
Tidskriftsartikel (refereegranskat)abstract
- An extensive remodelling process, referred to as cervical ripening, takes place in the cervical tissue during pregnancy and labour. It is recognized as softening and dilation of the cervical canal, and starts as a slow process during pregnancy, becoming rapid close to partum. In this study we focus on cytokines as possible mediators of this final remodelling. mRNA levels for interleukin (IL)-8, IL-6 and granulocyte colony-stimulating factor (G-CSF) were upregulated in the ripe postpartum cervical tissue (n = 8) compared to the unripe state (n = 9). Likewise, released cytokine concentrations increased from non-pregnant (n = 11) to the term-pregnant group (n = 13) with a further increase at partum (n = 16). IL-8 concentrations increased 4-fold from non-pregnant to term-pregnant (P<0.01), and a further 10-fold to postpartum state (P<0.0001). Concentrations of IL-6 and G-CSF were similarly increased. Specific IL-8 immunostaining was identified in the epithelia of pregnant cervical tissue (n = 7) and was most pronounced in the epithelia and stroma of postpartum tissue (n = 4). In conclusion, IL-8, IL-6 and G-CSF increase in the human cervix during the ripening process, indicating their important role in the cervical remodelling. These data demonstrate that cervical ripening is similar to an inflammatory process.
|
|
| 20. |
|
|
| 21. |
- Steiner, Svava E., et al.
(författare)
-
Effect of anticoagulant and platelet inhibition on the risk of bacteremia among patients with acute pyelonephritis : a retrospective cohort study
- 2022
-
Ingår i: BMC Infectious Diseases. - : Springer Nature. - 1471-2334. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background An increasing number of patients are being prescribed anticoagulants and platelet inhibitors (antithrombotic treatment). Basic research has suggested an association between antithrombotic treatment and bacteremia during kidney infection. Here, we investigated the association between antithrombotic treatment, bacteremia and acute kidney injury in patients with acute pyelonephritis. Methods A retrospective cohort study was conducted in a large university hospital in Sweden. Data were retrieved from electronic medical records for adult patients with acute pyelonephritis in 2016. The main outcome was bacteremia and secondary outcome acute kidney injury. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated through multiple logistic regression. Treatment with different groups of antithrombotic agents were compared to no antithrombotic treatment. Results 1814 patients with acute pyelonephritis were included, in whom bacteremia developed in 336 (18.5%). Low-molecular-weight heparin (LMWH) at prophylactic doses was associated with a lower risk of bacteremia, compared to no antithrombotic treatment (OR 0.5; 95% CI 0.3-0.7). Other antithrombotic treatments were not associated with a risk of bacteremia. Additionally, patients with prophylactic doses of LMWH had a lower risk of acute kidney injury (OR 0.5; 95% CI 0.3-0.8). Conclusions We found no association between antithrombotic treatment and an increased risk of bacteremia during acute pyelonephritis. Conversely, patients with prophylactic doses of LMWH had a slightly reduced risk of bacteremia. LMWH at prophylactic doses was also associated with a lower risk of acute kidney injury. Our results suggest that it is safe to continue antithrombotic treatment during acute pyelonephritis, in regards to bacteremia and acute kidney injury risk.
|
|
| 22. |
- Veses-Garcia, Marta, et al.
(författare)
-
Rapid Phenotypic Antibiotic Susceptibility Testing of Uropathogens Using Optical Signal Analysis on the Nanowell Slide
- 2018
-
Ingår i: Frontiers in Microbiology. - : FRONTIERS MEDIA SA. - 1664-302X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Achieving fast antimicrobial susceptibility results is a primary goal in the fight against antimicrobial resistance. Standard antibiotic susceptibility testing (AST) takes, however, at least a day from patient sample to susceptibility profile. Here, we developed and clinically validated a rapid phenotypic AST based on a miniaturized nanotiter plate, the nanowell slide, that holds 672 wells in a 500 nl format for bacterial cultivation. The multitude of nanowells allows multiplexing with a panel of six antibiotics relevant for urinary tract infections. Inclusion of seven concentrations per antibiotic plus technical replicates enabled us to determine a precise minimum inhibitory concentration for 70 clinical uropathogenic Escherichia coil isolates. By combining optical recordings of bacterial growth with an algorithm for optical signal analysis, we calculated T-lag, the point of transition from lag to exponential phase, in each nanoculture. Algorithm-assisted analysis determined antibiotic susceptibility as early as 3 h 40 min. In comparison to standard disk diffusion assays, the nanowell AST showed a total categorical agreement of 97.9% with 2.6% major errors and 0% very major errors for all isolate-antibiotic combination tested. Taking advantage of the optical compatibility of the nanowell slide, we performed microscopy to illustrate its potential in defining susceptibility profiles based on bacterial morphotyping. The excellent clinical performance of the nanowell AST, combined with a short detection time, morphotyping, and the very low consumption of reagents clearly show the advantage of this phenotypic AST as a diagnostic tool in a clinical setting.
|
|
| 23. |
|
|
| 24. |
- Weibull, Emilie, et al.
(författare)
-
Bacterial Nanoscale Cultures for Phenotypic Multiplexed Antibiotic Susceptibility Testing
- 2014
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 52:9, s. 3310-3317
-
Tidskriftsartikel (refereegranskat)abstract
- An optimal antimicrobial drug regimen is the key to successful clinical outcomes of bacterial infections. To direct the choice of antibiotic, access to fast and precise antibiotic susceptibility profiling of the infecting bacteria is critical. We have developed a high-throughput nanowell antibiotic susceptibility testing (AST) device for direct, multiplexed analysis. By processing in real time the optical recordings of nanoscale cultures of reference and clinical uropathogenic Escherichia coli strains with a mathematical algorithm, the time point when growth shifts from lag phase to early logarithmic phase (T-lag) was identified for each of the several hundreds of cultures tested. Based on T-lag, the MIC could be defined within 4 h. Heatmap presentation of data from this high-throughput analysis allowed multiple resistance patterns to be differentiated at a glance. With a possibility to enhance multiplexing capacity, this device serves as a high-throughput diagnostic tool that rapidly aids clinicians in prescribing the optimal antibiotic therapy.
|
|
| 25. |
- White, John Kerr, et al.
(författare)
-
A stable cyclized antimicrobial peptide derived from LL-37 with host immunomodulatory effects and activity against uropathogens
- 2022
-
Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 79:8
-
Tidskriftsartikel (refereegranskat)abstract
- The increasing antibiotic resistance among uropathogenic bacteria warrants alternative therapeutic strategies. We demonstrate the potential of the synthetic peptide CD4-PP, designed by dimerization and backbone cyclization of the shortest antimicrobial region of human cathelicidin, LL-37. CD4-PP is active against clinical and type strains of common uropathogens Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa at concentrations substantially below cellular cytotoxic levels and induced membrane deformation and leakage in E. coli and P. aeruginosa. Furthermore, CD4-PP treatment prevented the formation of new biofilm and dissolved mature biofilm created by E. coli and P. aeruginosa and targeted curli amyloid in E. coli biofilms. In addition, CD4-PP also induced production of LL-37 by uroepithelial cells and increased the expression of tight junction proteins claudin-14 and occludin. During uroepithelial cell infection, CD4-PP significantly reduced uropathogen survival when treatment was given at the start of infection. Low micromolar of CD4-PP treatment initiated after 2 h was successful with all tested species, except P. aeruginosa where CD4-PP was unable to reduce survival, which could be attributed by early biofilm formation. Finally, we demonstrated that urinary catheter pieces coated with saline fluid supplemented with CD4-PP reduced the attachment of E. coli, giving it a potential clinical application.
|
|
