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Berlin Brandenburg

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  • 1
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e36298
    Description: Lactobacillus- dominated vaginal microbiotas are associated with reproductive health and STI resistance in women, whereas altered microbiotas are associated with bacterial vaginosis (BV), STI risk and poor reproductive outcomes. Putative vaginal taxa have been observed in male first-catch urine, urethral swab and coronal sulcus (CS) specimens but the significance of these observations is unclear. We used 16 S rRNA sequencing to characterize the microbiota of the CS and urine collected from 18 adolescent men over three consecutive months. CS microbiotas of most participants were more stable than their urine microbiotas and the composition of CS microbiotas were strongly influenced by circumcision. BV-associated taxa, including Atopobium , Megasphaera , Mobiluncus , Prevotella and Gemella , were detected in CS specimens from sexually experienced and inexperienced participants. In contrast, urine primarily contained taxa that were not abundant in CS specimens. Lactobacilllus and Streptococcus were major urine taxa but their abundance was inversely correlated. In contrast, Sneathia , Mycoplasma and Ureaplasma were only found in urine from sexually active participants. Thus, the CS and urine support stable and distinct bacterial communities. Finally, our results suggest that the penis and the urethra can be colonized by a variety of BV-associated taxa and that some of these colonizations result from partnered sexual activity.
    Keywords: Research Article ; Biology ; Medicine ; Public Health And Epidemiology ; Infectious Diseases ; Microbiology ; Urology
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: Disease models & mechanisms, 01 April 2017, Vol.10(4), pp.425-437
    Description: Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here, we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. Distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J and C57BL/6J mice over 1 year after graded doses of whole-thorax lung irradiation (WTLI). Separately, comparison of gene expression profiles in lung tissue 24 h post-exposure demonstrated 〉5000 genes to be differentially expressed (twofold change) between strains with early versus late onset of disease. An immediate divergence in early tissue response between radiation-sensitive and -resistant strains was observed. In pneumonitis-prone C57L/J mice, differentially expressed genes were enriched in proinflammatory pathways, whereas in fibrosis-prone C57BL/6J mice, genes were enriched in pathways involved in purine and pyrimidine synthesis, DNA replication and cell division. At 24 h post-WTLI, different patterns of cellular damage were observed at the ultrastructural level among strains but microscopic damage was not yet evident under light microscopy. These data point toward a fundamental difference in patterns of early pulmonary tissue response to WTLI, consistent with the macroscopic expression of injury manifesting weeks to months after exposure. Understanding the mechanisms underlying development of RILD might lead to more rational selection of therapeutic interventions to mitigate healthy tissue damage.
    Keywords: Gene Expression Profiling ; Lung Fibrosis ; Murine Strain Differences ; Radiation Pneumonitis ; Disease Progression ; Gene Expression Profiling ; Lung Diseases -- Genetics ; Radiation Injuries -- Genetics
    ISSN: 17548403
    E-ISSN: 1754-8411
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  • 3
    Language: English
    In: BMC microbiology, 24 June 2014, Vol.14, pp.166
    Description: Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.
    Keywords: Bacterial Outer Membrane Proteins -- Metabolism ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Pathogenicity ; Virulence Factors -- Metabolism
    E-ISSN: 1471-2180
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  • 4
    Language: English
    In: Sports medicine (Auckland, N.Z.), July 2018, Vol.48(7), pp.1761
    Description: The article Test-Retest Reliability and Interpretation of Common Concussion Assessment Tools.
    Keywords: Medicine & Public Health ; Sports Medicine ; Medicine;
    ISSN: 01121642
    E-ISSN: 1179-2035
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  • 5
    Language: English
    In: The Journal of infectious diseases, 01 January 2010, Vol.201(1), pp.42-51
    Description: Repeated Chlamydia trachomatis infections are common among young sexually active women. The relative frequency of reinfection and antibiotic treatment failure is undefined. Adolescent women enrolled in a longitudinal cohort had behavioral and sexually transmitted infection assessments performed every 3 months, including amplification tests for C. trachomatis, ompA genotyping, and interviews and diary entries to document sex partner-specific coitus and event-specific condom use. Repeated infections were classified as reinfection or treatment failure by use of an algorithm. All infections for which treatment outcomes were known were used to estimate the effectiveness of antibiotic use. We observed 478 episodes of infection among 210 study participants; 176 women remained uninfected. The incidence rate was 34 episodes/100 woman-years. Of the women who were infected, 121 experienced 1 repeated infections, forming 268 episode pairs; 183 pairs had complete data available and were classified using the algorithm. Of the repeated infections, 84.2% were definite, probable, or possible reinfections; 13.7% were probable or possible treatment failures; and 2.2% persisted without documented treatment. For 318 evaluable infections, we estimated 92.2% effectiveness of antibiotic use. Most repeated chlamydial infections in this high-incidence cohort were reinfections, but repeated infections resulting from treatment failures occurred as well. Our results have implications for male screening and partner notification programs and suggest the need for improved antibiotic therapies.
    Keywords: Anti-Bacterial Agents -- Therapeutic Use ; Azithromycin -- Therapeutic Use ; Chlamydia Infections -- Drug Therapy
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 6
    Language: English
    In: The Journal of infectious diseases, 15 June 2011, Vol.203(12), pp.1859-65
    Description: Haemophilus ducreyi 35000HP contains a homolog of the CpxRA 2-component signal transduction system, which controls the cell envelope stress response system in other gram-negative bacteria and regulates some important H. ducreyi virulence factors. A H. ducreyi cpxR mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule formation rate in 5 volunteers was 33% (95% confidence interval [CI], 1.3%-65.3%) at 15 parent sites and 40% (95% CI, 18.1%-61.9%) at 15 mutant sites (P = .35). Thus, the cpxR mutant was not attenuated for virulence. Inactivation of the H. ducreyi cpxR gene did not reduce the ability of this mutant to express certain proven virulence factors, including the DsrA serum resistance protein and the LspA2 protein, which inhibits phagocytosis. These results expand our understanding of the involvement of the CpxRA system in regulating virulence expression in H. ducreyi.
    Keywords: Bacterial Proteins -- Genetics ; Chancroid -- Microbiology ; Haemophilus Ducreyi -- Genetics
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 7
    Language: English
    In: The Journal of infectious diseases, November 2012, Vol.206(9), pp.1407-14
    Description: Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute-binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi's resistance to human defensins. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed.
    Keywords: Drug Resistance, Bacterial ; Antimicrobial Cationic Peptides -- Pharmacology ; Haemophilus Ducreyi -- Enzymology ; Membrane Transport Proteins -- Metabolism ; Virulence Factors -- Metabolism
    ISSN: 00221899
    E-ISSN: 1537-6613
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  • 8
    Language: English
    In: Infection and immunity, December 2012, Vol.80(12), pp.4426-34
    Description: During microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization during Haemophilus ducreyi infection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection with H. ducreyi in vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required for H. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity against H. ducreyi and similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute to H. ducreyi clearance during human infection.
    Keywords: Chancroid -- Immunology ; Haemophilus Ducreyi -- Immunology ; Interleukin-10 -- Immunology ; Macrophage Activation -- Immunology ; Macrophages -- Classification
    E-ISSN: 1098-5522
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  • 9
    Language: English
    In: Infection and immunity, August 2011, Vol.79(8), pp.3338-47
    Description: Haemophilus ducreyi causes chancroid, a genital ulcer disease. In human inoculation experiments, most volunteers fail to clear the bacteria despite the infiltration of innate and adaptive immune cells to the infected sites. The immunosuppressive protein indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine metabolic pathway. Tryptophan depletion and tryptophan metabolites contribute to pathogen persistence by inhibiting T cell proliferation, inducing T cell apoptosis, and promoting the expansion of FOXP3(+) regulatory T (Treg) cells. We previously found that FOXP3(+) Treg cells are enriched in experimental lesions and that H. ducreyi induced IDO transcription in dendritic cells (DC) derived from blood of infected volunteers who developed pustules. Here, we showed that enzymatically active IDO was induced in DC by H. ducreyi. Neutralizing antibodies against interferon alpha/beta receptor 2 chain (IFNAR2) and tumor necrosis factor alpha (TNF-α) inhibited IDO induction. Inhibitors of the mitogen-activated protein kinase (MAPK) p38 and nuclear factor-κB (NF-κB) also inhibited IDO expression. Neither bacterial contact with nor uptake by DC was required for IDO activation. H. ducreyi culture supernatant and H. ducreyi lipooligosaccharides (LOS) induced IDO expression, which required type I interferons, TNF-α, and the three MAPK (p38, c-Jun N-terminal kinase, and extracellular signal regulated kinase) and NF-κB pathways. In addition, LOS-induced IFN-β activated the JAK-STAT pathway. Blocking the LOS/Toll-like receptor 4 (TLR4) signaling pathway greatly reduced H. ducreyi-induced IDO production. These findings indicate that H. ducreyi-induced IDO expression in DC is largely mediated by LOS via type I interferon- and TNF-α-dependent mechanisms and the MAPK, NF-κB, and JAK-STAT pathways.
    Keywords: Immune Tolerance ; Dendritic Cells -- Immunology ; Haemophilus Ducreyi -- Immunology ; Indoleamine-Pyrrole 2,3,-Dioxygenase -- Biosynthesis ; Interferon Type I -- Metabolism ; Lipopolysaccharides -- Immunology ; Tumor Necrosis Factor-Alpha -- Metabolism
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 10
    Language: English
    In: The Journal of infectious diseases, 15 June 2010, Vol.201(12), pp.1839-48
    Description: Haemophilus ducreyi causes chancroid, a genital ulcer disease. Among human volunteers, the majority of experimentally infected individuals fail to clear the infection and form pustules. Here, we investigated the role played by CD4(+)FOXP3(+) regulatory T (T(reg)) cells in the formation of pustules. In pustules, there was a significant enrichment of CD4(+)FOXP3(+) T cells, compared with that in peripheral blood. The majority of lesional FOXP3(+) T cells were CD4(+), CD25(+), CD127(lo/-), and CTLA-4(+). FOXP3(+) T cells were found throughout pustules but were most abundant at their base. Significantly fewer lesional CD4(+)FOXP3(+) T cells expressed interferon gamma, compared with lesional CD4(+)FOXP3(-) effector T cells. Depletion of CD4(+)CD25(+) T cells from the peripheral blood of infected and uninfected volunteers significantly enhanced proliferation of H. ducreyi-reactive CD4(+) T cells. Our results indicate that the population of CD4(+)CD25(+)CD127(lo/-)FOXP3(+) T(reg) cells are expanded at H. ducreyi-infected sites and that these cells may play a role in suppressing the host immune response to the bacterium.
    Keywords: Immune Tolerance ; Cd4-Positive T-Lymphocytes -- Immunology ; Forkhead Transcription Factors -- Analysis ; Haemophilus Infections -- Immunology ; Haemophilus Ducreyi -- Immunology ; T-Lymphocytes, Regulatory -- Immunology
    ISSN: 00221899
    E-ISSN: 1537-6613
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