| 44711. |
- Carvalheira, A., et al.
(författare)
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Acinetobacter portensis sp. Nov. and acinetobacter guerrae sp. nov., isolated from raw meat
- 2020
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Ingår i: International journal of systematic and evolutionary microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 70:8, s. 4544-4554
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Tidskriftsartikel (refereegranskat)abstract
- The taxonomic status of six strains of Acinetobacter obtained from meat samples, collected from supermarkets in Porto, Por-tugal, was investigated using polyphasic analysis. Partial rpoB sequence similarities lower than 95 % to other Acinetobacter species with validly published names led to the hypothesis that these strains represented novel species. This was confirmed based on comparative multilocus sequence analysis, which included the gyrB, recA and 16S rRNA genes, revealing that these strains represented two coherent lineages that were distinct from each other and from all known species. The names Acine-tobacter portensis sp. nov. (comprising four strains) and Acinetobacter guerrae sp. nov. (comprising two strains) are proposed for these novel species. The species status of these two groups was confirmed by low (below 95 %) whole-genome sequence average nucleotide identity values and low (below 70 %) digital DNA–DNA hybridization similarities between the whole-genome sequences of the proposed type strains of each novel species and the representatives of the known Acinetobacter species. Phylogenomic treeing from core genome analysis supported these results. The coherence of each new species lineage was supported by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry differentiation of the species at the protein level, by cellular fatty acid profiles, and by unique and differential combinations of metabolic and physiological properties shared by each novel species. The type strain of A. portensis sp. nov. is AC 877T (=CCUG 68672T=CCM 8789T) and the type strain of A. guerrae sp. nov. is AC 1271T (=CCUG 68674T=CCM 8791T). © 2020 The Authors.
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| 44712. |
- Carvalho, Maria da Glória S, et al.
(författare)
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Designation of the provisional new enterococcus species CDC PNS-E2 as Enterococcus sanguinicola sp. nov., isolated from human blood, and identification of a strain previously named Enterococcus CDC PNS-E1 as Enterococcus italicus Fortina, Ricci, Mora, and Manachini 2004.
- 2008
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Ingår i: Journal of clinical microbiology. - 1098-660X. ; 46:10, s. 3473-3476
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Tidskriftsartikel (refereegranskat)abstract
- We have previously characterized two new enterococcal species (provisionally designated CDC PNS-E1 and CDC PNS-E2) recovered from clinically significant specimens associated with invasive infections in humans. In the present report we provide additional data and propose formal denominations for isolates of these two species of Enterococcus. Results of 16S rRNA gene sequencing, sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of whole-cell protein profiles, and DNA-DNA reassociation experiments indicated that the blood isolate ATCC BAA-780 (SS 1728; CDC PNS-E1) corresponds to Enterococcus italicus, whose species epithet was proposed to designate isolates from artisanal Italian cheese. Strain ATCC BAA-781 (CCUG 47861; SS 1729; CDC PNS-E2), a vancomycin-resistant isolate recovered from the blood of a patient in the United States, was found to be highly related at the species level to another blood isolate (SS 1743; CCUG 47884) from Sweden, and for these we propose the designation Enterococcus sanguinicola sp. nov.
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| 44713. |
- Casabona, Giacomo, et al.
(författare)
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Randomised controlled trial showed long-term efficacy, immunogenicity and safety of varicella vaccines in Norwegian and Swedish children
- 2022
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 111:2, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Several countries, such as Norway and Sweden, have not implemented universal varicella vaccination. We present data for Norway and Sweden that were generated by a paediatric multi-country Phase III study over a 10-year period. This assessed the efficacy, antibody persistence and safety of two varicella vaccines containing the same Oka strain.Methods: This was an observer-blind, controlled trial conducted in 10 European countries. Children aged 12–22 months (n = 5803) were randomised 3:3:1 and vaccinated between 1 September 2005 and 10 May 2006. The two-dose group received two tetravalent measles-mumps-rubella-varicella vaccine doses. The one-dose group received one monovalent varicella vaccine dose after a measles-mumps-rubella vaccine dose. Control group participants received two measles-mumps-rubella vaccine doses. Main study outcomes were vaccine efficacy against confirmed varicella cases and incidence of adverse events.Results: Vaccine efficacy in the two-dose group was ≥92.1% in both Norwegian and Swedish children compared to 72.3% in Norway and 58.0% in Sweden in the one-dose group. Incidences of adverse events and serious adverse events were similar in the Norwegian and Swedish study populations.Conclusion: Consistent with overall study results, high efficacy against varicella and acceptable safety profiles of the two varicella vaccines were observed in Norwegian and Swedish populations. These findings highlight the benefits of varicella vaccines, particularly when administered as a two-dose schedule.
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| 44714. |
- Casado-Bedmar, Maite, et al.
(författare)
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Elevated F-EDN correlates with mucosal eosinophil degranulation in patients with IBS : A possible association with microbiota?
- 2022
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Ingår i: Journal of Leukocyte Biology. - : Alan R. Liss Inc.. - 0741-5400 .- 1938-3673. ; 111:3, s. 655-665
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils have been linked to functional dyspepsia; however, less is known about their role in irritable bowel syndrome (IBS). This study tested the hypothesis of alterations in levels of fecal eosinophil-derived neurotoxin (F-EDN) and eosinophil density and degranulation within the colonic mucosa of IBS patients compared with healthy controls (HC). Colonic biopsies were collected from 37 IBS patients and 20 HC and analyzed for eosinophil numbers and local degranulation of eosinophil cationic protein (ECP) by histologic procedures. Fecal samples were collected for F-EDN and microbiota analysis. Differentiated 15HL-60 cells were used in vitro to investigate the direct effect of live bacteria on eosinophil activation measured by a colorimetric assay with o-phenylenediamine (OPD) substrate. We observed a higher number of eosinophils and increased extracellular ECP in the mucosa of IBS patients compared with HC. Moreover, F-EDN levels in IBS samples were elevated compared with HC and positively correlated to extracellular ECP. Metagenomic analysis showed significant correlations between bacterial composition and eosinophil measurements in both HC and IBS patients. In vitro experiments revealed an increased degranulation of 15HL-60 after stimulation with Salmonella typhimurium, Salmonella enterica, and Yersinia enterocolitica. To conclude, we could demonstrate alterations related to eosinophils in IBS, and, for the first time, a positive correlation between F-EDN levels and degranulated eosinophils in the colonic mucosa of IBS patients. Together our results suggest that eosinophils play a role in the pathophysiology of IBS and the mechanisms might be linked to an altered microbiota.
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| 44715. |
- Casado Bedmar, Maria Teresa, 1990-
(författare)
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Neuro-immuno-regulation of inflammation in the colonic mucosa : Focus on mast cells and eosinophils in bowel disorders
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Intestinal homeostasis is key to control uptake across the mucosa and protect from harmful substances. Disturbances in the bidirectional communication between the gut and the brain are implicated in irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD), being Crohn’s disease (CD) and ulcerative colitis (UC) the two most common IBD subtypes. Although these chronic bowel-relapsing inflammatory disorders present different histopathology, they share similar pathological features. Both IBS and IBD are characterized by a disrupted intestinal barrier function, a pro-inflammatory chronic condition, and an altered gut-brain axis. Despite all the scientific effort, the sequence or exact combination of events that drive these diseases are still unknown, and so is the exact role of every single component. Growing evidence suggests altered neuro-immune interactions as a pathogenic factor.The general aim of this thesis was to elucidate the potential involvement of mast cells and eosinophils in IBS and IBD, and the neuro-immune intercellular circuit via vasoactive intestinal polypeptide (VIP) that might exacerbate mucosal inflammation and intestinal barrier disruption.Intestinal tissues from IBS, inactive IBD, healthy controls (HC), and murine colitis were collected. Electrophysiological and permeability studies were performed using the ex vivo Ussing chamber technique. Tissues were processed with immunohistological procedures to study cell numbers, activation, location, and interactions in relation to VIP.We demonstrated for the very first time an increased transcellular passage of live commensal and pathogenic bacteria through the colonic mucosa of IBS, identifying VIP as a key regulatory molecule together with mast cells activation. In vitro experiments revealed the ability of VIP to activate mast cells. Image analysis identified VIP-mast cells in closer proximity in IBD patients and murine colitis compared to controls. Communication between mast cells and VIP was shown upregulated in IBD and mice colitis via VIP receptor (VPAC)1. Similarities and differences between HC, IBS, and IBD were further studied. Results indicated a pronounced increased intestinal permeability in UC, even during remission, followed by IBS, compared to healthy controls. Surprisingly, permeability results did not correlate with mast cells, but with eosinophil number and activation. A further image analysis suggested an inhibitory effect of eosinophils and VIP on mast cells and an altered interaction between them under inflammatory conditions. Lastly, intestinal VIP levels were shown to increase in IBD patients after the treatment with biological agents and were suggested as a possible biomarker for biological treatment outcome.This thesis presents novel insights into the regulation of intestinal permeability, as well as into the pathophysiology of IBD and IBS by demonstrating the importance of neuro-immune interactions between mast cells, VIP, and eosinophils.Altogether, our findings have broadened the knowledge of neuro-immune interactions in IBS and IBD and might have the potential to onsight lead to new therapeutic approaches thereby improving the outcomes for patients suffering from these diseases.
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| 44716. |
- Casas, Rosaura, et al.
(författare)
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Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 μg GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD65-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC < 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8+ T cells activation. Patients with poorer clinical response had higher baseline levels of GAD65-induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment.
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| 44717. |
- Caselli, Lucrezia, et al.
(författare)
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Skin and wound delivery systems for antimicrobial peptides
- 2023
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Ingår i: Current Opinion in Colloid and Interface Science. - 1359-0294. ; 65
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Forskningsöversikt (refereegranskat)abstract
- Non-healing wounds cause hundreds of thousands of deaths every year, and result in large costs for society. A key reason for this is the prevalence of challenging bacterial infections, which may dramatically hinder wound healing. With resistance development among bacteria against antibiotics, this situation has deteriorated during the last couple of decades, pointing to an urgent need for new wound treatments. In particular, this applies to wound dressings able to combat bacterial infection locally in wounds and impaired skin, including those formed by bacteria resistant to conventional antibiotics. Within this context, antimicrobial peptides (AMPs) are currently receiving intense interest. AMPs are amphiphilic peptides, frequently net positively charged, and with a sizable fraction of hydrophobic amino acids. Through destabilization of bacterial membranes, neutralization of inflammatory lipopolysaccharides, and other mechanisms, AMPs can be designed for potent antimicrobial effects, also against antibiotics-resistant strains, and to provide immunomodulatory effects while simultaneously displaying low toxicity. While considerable attention has been placed on AMP optimization and clarification of their mode(s)-of-action, much less attention has been paid on efficient AMP delivery. Considering that AMPs are large molecules, net positively charged, amphiphilic, and susceptible to infection-mediated proteolytic degradation, efficient in vivo delivery of such peptides is, however, challenging and delivery systems needed for the realization of AMP-based therapeutics. In the present work, recent developments regarding AMP delivery systems for treatment of wounds and skin infections are discussed, with the aim to link results from physicochemical studies on, e.g., peptide loading/release, membrane interactions, and self-assembly, with those on the biological functional performance of AMP delivery systems in terms of antimicrobial effects, cell toxicity, inflammation, and wound healing.
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| 44718. |
- Casper, C, et al.
(författare)
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Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes
- 2002
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 18:5, s. 343-352
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Tidskriftsartikel (refereegranskat)abstract
- Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n=2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4 1 cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.
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| 44719. |
- Casper, C, et al.
(författare)
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Coreceptor usage of primary HIV type 1 isolates obtained from different lymph node subsets
- 2005
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 21:12, s. 1003-1010
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Tidskriftsartikel (refereegranskat)abstract
- Biological characteristics of virus quantitatively rescued from different cell types present in lymph nodes of HIV-1-infected individuals in various stages of their disease were determined, not including patients with AIDS defining illness. Viruses were obtained by cocultivation with donor monocyte-derived macrophages and T-lymphocytes and their biological phenotype compared to viruses obtained from the peripheral blood mononuclear cells of the same patient. The biological phenotype was determined on established cell lines (U937-2, CEM, and MT-2) and on the U87.CD4 coreceptor indicator cell lines and variable region 3 (V3) of the envelope was subjected to direct sequencing. All isolates obtained from lymph node subsets used CCR5 as coreceptor. Furthermore, these viruses were also sensitive to inhibition by beta-chemokines as analyzed for viruses of one patient. All 12 V3 regions showed a unique sequence indicating compartmentalization within each patient. The biological phenotype of CCR5-dependent (R5) HIV-1 isolates obtained from PBMC resembles the phenotype of viruses isolated from different lymph node cell subsets.
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| 44720. |
- Castanheira, Sonia, et al.
(författare)
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A Specialized Peptidoglycan Synthase Promotes Salmonella Cell Division inside Host Cells
- 2017
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Ingår i: mBio. - 2161-2129 .- 2150-7511. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial cell division has been studied extensively under laboratory conditions. Despite being a key event in the bacterial cell cycle, cell division has not been explored in vivo in bacterial pathogens interacting with their hosts. We discovered in Salmonella enterica serovar Typhimurium a gene absent in nonpathogenic bacteria and encoding a peptidoglycan synthase with 63% identity to penicillin-binding protein 3 (PBP3). PBP3 is an essential cell division-specific peptidoglycan synthase that builds the septum required to separate daughter cells. Since S. Typhimurium carries genes that encode a PBP3 paralog-which we named PBP3(SAL)-and PBP3, we hypothesized that there are different cell division events in host and nonhost environments. To test this, we generated S. Typhimurium isogenic mutants lacking PBP3(SAL) or the hitherto considered essential PBP3. While PBP3 alone promotes cell division under all conditions tested, the mutant producing only PBP3(SAL) proliferates under acidic conditions (pH <= 5.8) but does not divide at neutral pH. PBP3(SAL) production is tightly regulated with increased levels as bacteria grow in media acidified up to pH 4.0 and in intracellular bacteria infecting eukaryotic cells. PBP3(SAL) activity is also strictly dependent on acidic pH, as shown by beta-lactam antibiotic binding assays. Live-cell imaging microscopy revealed that PBP3(SAL) alone is sufficient for S. Typhimurium to divide within phagosomes of the eukaryotic cell. Additionally, we detected much larger amounts of PBP3(SAL) than those of PBP3 in vivo in bacteria colonizing mouse target organs. Therefore, PBP3(SAL) evolved in S. Typhimurium as a specialized peptidoglycan synthase promoting cell division in the acidic intraphagosomal environment. IMPORTANCE During bacterial cell division, daughter cells separate by a transversal structure known as the division septum. The septum is a continuum of the cell wall and therefore is composed of membrane(s) and a peptidoglycan layer. To date, actively growing bacteria were reported to have only a "cell division-specific" peptidoglycan synthase required for the last steps of septum formation and consequently, essential for bacterial life. Here, we discovered that Salmonella enterica has two peptidoglycan synthases capable of synthesizing the division septum. One of these enzymes, PBP3(SAL), is present only in bacterial pathogens and evolved in Salmonella to function exclusively in acidic environments. PBP3(SAL) is used preferentially by Salmonella to promote cell division in vivo in mouse target organs and inside acidified phagosomes. Our data challenge the concept of only one essential cell division-specific peptidoglycan synthase and demonstrate that pathogens can divide in defined host locations using alternative mechanisms.
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