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Berlin Brandenburg

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  • Article  (12)
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  • Article  (12)
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  • 1
    In: The Journal of Infectious Diseases, 2017, Vol. 215(4), pp.653-657
    Description: Staphylococcus aureus, a metabolically flexible gram-positive pathogen, causes infections in a variety of tissues. Recent evidence implicates S. aureus as an emerging cause of chorioamnionitis and premature rupture of membranes, which are associated with preterm birth and neonatal disease. We demonstrate here that S. aureus infects and forms biofilms on the choriodecidual surface of explanted human gestational membranes. Concomitantly, S. aureus elicits the production of proinflammatory cytokines, which could ultimately perturb maternal-fetal tolerance during pregnancy. Therefore, targeting the immunological response to S. aureus infection during pregnancy could attenuate disease among infected individuals, especially in the context of antibiotic resistance.
    Keywords: 〈Kwd〉 〈Italic Toggle="Yes"〉Staphylococcus Aureus〈/Italic〉 〈/Kwd〉 ; Gestational Membranes ; Cytokine
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 2
    Language: English
    In: Journal of Innate Immunity, February 2018, Vol.10(1), pp.3-13
    Description: Tissue macrophages are derived from either circulating blood monocytes that originate in the bone marrow, or embryonic precursors that establish residence in tissues and are maintained independent of bone marrow progenitors. Macrophages perform diverse functions including tissue repair, the maintenance of homeostasis, and immune regulation. Recent studies have demonstrated that macrophages produce extracellular traps (ETs). ETs are an immune response by which a cell undergoes “ETosis” to release net-like material, with strands composed of cellular DNA that is studded with histones and cellular proteins. ETs are thought to immobilize and kill microorganisms, but also been implicated in disease pathology including aseptic inflammation and autoimmune disease. We conducted a scoping review to define what is known from the existing literature about the ETs produced by monocytes or macrophages. The results suggest that macrophage ETs (METs) are produced in response to various microorganisms and have similar features to neutrophil ETs (NETs), in that METs are produced by a unique cell death program (METosis), which results in release of fibers composed of DNA and studded with cellular proteins. METs function to immobilize and kill some microorganisms, but may also play a role in disease pathology.
    Keywords: Review ; Macrophage ; Extracellular Traps ; Metosis ; Biology
    ISSN: 1662-811X
    E-ISSN: 1662-8128
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  • 3
    Language: English
    In: mBio, 01 November 2018, Vol.9(6), p.e02084-18
    Description: Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a common pathogen during pregnancy where infection can result in chorioamnionitis, preterm premature rupture of membranes (PPROM), preterm labor, stillbirth, and neonatal sepsis. Mechanisms by which GBS infection results...
    Keywords: Streptococcus Agalactiae ; Extracellular Traps ; Group B Streptococcus ; Macrophages ; Matrix Metalloproteinase ; Biology
    ISSN: 21612129
    E-ISSN: 2150-7511
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  • 4
    Language: English
    In: The Journal of infectious diseases, 01 March 2009, Vol.199(5), pp.684-92
    Description: A gene expression study of Haemophilus ducreyi identified the hypothetical lipoprotein HD0192, renamed here "fibrinogen binder A" (FgbA), as being preferentially expressed in vivo. To test the role played by fgbA in virulence, an isogenic fgbA mutant (35000HPfgbA) was constructed using H. ducreyi 35000HP, and 6 volunteers were experimentally infected with 35000HP or 35000HPfgbA. The overall pustule-formation rate was 61.1% at parent sites and 22.2% at mutant sites (P = .019). Papules were significantly smaller at mutant sites than at parent sites (13.3 vs. 37.9 mm(2); P = .002) 24 h after inoculation. Thus, fgbA contributed significantly to the virulence of H. ducreyi in humans. In vitro experiments demonstrated that fgbA encodes a fibrinogen-binding protein; no other fibrinogen-binding proteins were identified in 35000HP. fgbA was conserved among clinical isolates of both class I and II H. ducreyi strains, supporting the finding that fgbA is important for H. ducreyi infection.
    Keywords: Bacterial Proteins -- Metabolism ; Chancroid -- Microbiology ; Fibrinogen -- Metabolism ; Haemophilus Ducreyi -- Genetics ; Lipoproteins -- Metabolism
    ISSN: 0022-1899
    E-ISSN: 15376613
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  • 5
    Language: English
    In: Frontiers in Microbiology, 01 August 2018, Vol.9
    Description: One elusive area in the Helicobacter pylori field is an understanding of why some infections result in gastric cancer, yet others persist asymptomatically for the life-span of the individual. Even before the genomic era, the high level of intraspecies diversity of H. pylori was well recognized...
    Keywords: Homb ; Arsrs ; H. Pylori ; Biofilms ; Omps ; Biology
    E-ISSN: 1664-302X
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  • 6
    Language: English
    In: ACS infectious diseases, 11 August 2017, Vol.3(8), pp.595-605
    Description: Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive bacterial pathogen that causes invasive infections in both children and adults. During pregnancy, GBS is a significant cause of infection of the fetal membranes (chorioamnionitis), which can lead to intra-amniotic infection, preterm birth, stillbirth, and neonatal sepsis. Recently, breastfeeding has been thought to represent a potential mode of GBS transmission from mother to newborn, which might increase the risk for late-onset sepsis. Little is known, however, about the molecular components of breast milk that may support or prevent GBS colonization. In this study, we examine how human milk oligosaccharides (HMOs) affect the pathogenesis of GBS. HMOs from discrete donor samples were isolated and profiled by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Growth and biofilm assays show that HMOs from mothers of specific milk groups can modulate the growth and biofilm formation of GBS. High-resolution field-emission gun scanning electron microscopy (SEM) and confocal laser scanning microscopy confirmed the quantitative biofilm assays and demonstrated cell arrangement perturbations in bacterial cultures treated with specific oligosaccharides. These findings demonstrate that HMOs affect the growth and cell biology of GBS. Finally, this study provides the first example of HMOs functioning as antibiofilm agents against GBS.
    Keywords: GBS ; Group B Streptococcus ; HMO ; Antibiofilm ; Antimicrobial ; Bacteriostatic ; Human Milk Oligosaccharides ; Anti-Bacterial Agents -- Pharmacology ; Biofilms -- Drug Effects ; Milk, Human -- Chemistry ; Oligosaccharides -- Pharmacology ; Streptococcus Agalactiae -- Drug Effects
    E-ISSN: 2373-8227
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  • 7
    Language: English
    In: ACS infectious diseases, 09 March 2018, Vol.4(3), pp.315-324
    Description: In a previous study, we reported that human milk oligosaccharides (HMOs) isolated from five donor milk samples possessed antimicrobial and antibiofilm activity against Streptococcus agalactiae, also known as Group B Streptococcus or GBS. Herein, we present a broader evaluation of the antimicrobial and antibiofilm activity by screening HMOs from 14 new donors against three strains of GBS and two of the ESKAPE pathogens of particular interest to child health, Staphylococcus aureus and Acinetobacter baumannii. Growth and biofilm assays showed that HMOs from these new donors possessed antimicrobial and antibiofilm activity against all three strains of GBS, antibiofilm activity against methicillin-resistant S. aureus strain USA300, and antimicrobial activity against A. baumannii strain ATCC 19606.
    Keywords: A. baumannii ; GBS ; S. agalactiae ; S. aureus ; Antibiofilm ; Antimicrobial
    E-ISSN: 2373-8227
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  • 8
    In: American Journal of Reproductive Immunology, October 2018, Vol.80(4), pp.n/a-n/a
    Description: Bacterial chorioamnionitis causes adverse pregnancy outcomes, yet host-microbial interactions are not well characterized within gestational membranes. The decidua, the outermost region of the membranes, is a potential point of entry for bacteria ascending from the vagina to cause chorioamnionitis. We sought to determine whether paracrine communication between decidual stromal cells and macrophages shaped immune responses to microbial sensing. Decidual cell-macrophage interactions were modeled in vitro utilizing decidualized, telomerase-immortalized human endometrial stromal cells (dTHESCs) and phorbol ester-differentiated THP-1 macrophage-like cells. The production of inflammatory mediators in response to LPS was monitored by ELISA for both cell types, while phagocytosis of bacterial pathogens (Escherichia coli and Group B Streptococcus (GBS)) was measured in THP-1 cells or primary human placental macrophages. Diclofenac, a non-selective cyclooxygenase inhibitor, and prostaglandin E (PGE ) were utilized to interrogate prostaglandins as decidual cell-derived paracrine immunomodulators. A mouse model of ascending chorioamnionitis caused by GBS was utilized to assess the colocalization of bacteria and macrophages in vivo and assess PGE production. In response to LPS, dTHESC and THP-1 coculture demonstrated enhancement of most inflammatory mediators, but a potent suppression of macrophage TNF-α generation was observed. This appeared to reflect a paracrine-mediated effect of decidual cell-derived PGE . In mice with GBS chorioamnionitis, macrophages accumulated at sites of bacterial invasion with increased PGE in amniotic fluid, suggesting such paracrine effects might hold relevance in vivo. These data suggest key roles for decidual stromal cells in modulating tissue responses to microbial threat through release of PGE .
    Keywords: Chorioamnionitis ; Fetal Membranes ; Infection ; Microfluidics ; Pregnancy ; Prostaglandins
    ISSN: 1046-7408
    E-ISSN: 1600-0897
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  • 9
    Language: English
    In: Nature communications, 15 June 2016, Vol.7, pp.11951
    Description: Microorganisms form biofilms containing differentiated cell populations. To determine factors driving differentiation, we herein visualize protein and metal distributions within Pseudomonas aeruginosa biofilms using imaging mass spectrometry. These in vitro experiments reveal correlations between differential protein distribution and metal abundance. Notably, zinc- and manganese-depleted portions of the biofilm repress the production of anti-staphylococcal molecules. Exposure to calprotectin (a host protein known to sequester metal ions at infectious foci) recapitulates responses occurring within metal-deplete portions of the biofilm and promotes interaction between P. aeruginosa and Staphylococcus aureus. Consistent with these results, the presence of calprotectin promotes co-colonization of the murine lung, and polymicrobial communities are found to co-exist in calprotectin-enriched airspaces of a cystic fibrosis lung explant. These findings, which demonstrate that metal fluctuations are a driving force of microbial community structure, have clinical implications because of the frequent occurrence of P. aeruginosa and S. aureus co-infections.
    Keywords: Immunity, Innate ; Microbial Interactions ; Leukocyte L1 Antigen Complex -- Pharmacology ; Pseudomonas Aeruginosa -- Metabolism ; Staphylococcus Aureus -- Metabolism
    E-ISSN: 2041-1723
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  • 10
    Language: English
    In: Frontiers in cellular and infection microbiology, 2017, Vol.7, pp.19
    Description: , or Group B (GBS), is a gram-positive bacterial pathogen associated with infection during pregnancy and is a major cause of morbidity and mortality in neonates. Infection of the extraplacental membranes surrounding the developing fetus, a condition known as chorioamnionitis, is characterized histopathologically by profound infiltration of polymorphonuclear cells (PMNs, neutrophils) and greatly increases the risk for preterm labor, stillbirth, or neonatal GBS infection. The advent of animal models of chorioamnionitis provides a powerful tool to study host-pathogen relationships and . The purpose of this study was to evaluate the innate immune response elicited by GBS and evaluate how antimicrobial strategies elaborated by these innate immune cells affect bacteria. Our work using a mouse model of GBS ascending vaginal infection during pregnancy reveals that clinically isolated GBS has the capacity to invade reproductive tissues and elicit host immune responses including infiltration of PMNs within the choriodecidua and placenta during infection, mirroring the human condition. Upon interacting with GBS, murine neutrophils elaborate DNA-containing extracellular traps, which immobilize GBS and are studded with antimicrobial molecules including lactoferrin. Exposure of GBS to holo- or apo-forms of lactoferrin reveals that the iron-sequestration activity of lactoferrin represses GBS growth and viability in a dose-dependent manner. Together, these data indicate that the mouse model of ascending infection is a useful tool to recapitulate human models of GBS infection during pregnancy. Furthermore, this work reveals that neutrophil extracellular traps ensnare GBS and repress bacterial growth via deposition of antimicrobial molecules, which drive nutritional immunity via metal sequestration strategies.
    Keywords: Streptococcus Agalactiae ; Group B Streptococcus ; Metal ; Neutrophils ; Pregnancy ; Extracellular Traps ; Immunity, Innate ; Neutrophil Infiltration ; Mucous Membrane -- Pathology ; Reproductive Tract Infections -- Pathology ; Streptococcus Agalactiae -- Pathogenicity
    E-ISSN: 2235-2988
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