Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Infection and Immunity, American Society for Microbiology, Vol. 86, No. 7 ( 2018-07)
    Abstract: Some members of the genus Chlamydia , including the human pathogen Chlamydia trachomatis , infect multiple tissues, including the genital and gastrointestinal (GI) tracts. However, it is unknown if bacterial targeting to these sites is mediated by multifunctional or distinct chlamydial factors. We previously showed that disruption of individual large clostridial toxin homologs encoded within the Chlamydia muridarum plasticity zone were not critical for murine genital tract infection. Here, we assessed whether cytotoxin genes contribute to C. muridarum GI tropism. Infectivity and shedding of wild-type (WT) C. muridarum and three mutants containing nonsense mutations in different cytotoxin genes, tc0437 , tc0438 , and tc0439 , were compared in mouse genital and GI infection models. One mutant, which had a nonsense mutation in tc0439 , was highly attenuated for GI infection and had a GI 50% infectious dose (ID 50 ) that was 1,000 times greater than that of the WT. GI inoculation with this mutant failed to elicit anti-chlamydial antibodies or to protect against subsequent genital tract infection. Genome sequencing of the tc0439 mutant revealed additional chromosomal mutations, and phenotyping of additional mutants suggested that the GI attenuation might be linked to a nonsense mutation in tc0600 . The molecular mechanism underlying this dramatic difference in tissue-tropic virulence is not fully understood. However, isolation of these mutants demonstrates that distinct chlamydial chromosomal factors mediate chlamydial tissue tropism and provides a basis for vaccine initiatives to isolate chlamydia strains that are attenuated for genital infection but retain the ability to colonize the GI tract and elicit protective immune responses.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
    detail.hit.zdb_id: 1483247-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-06-30)
    Abstract: It is unknown if LPS (lipopolysaccharides) and markers of immune activation, soluble CD14 (sCD14) and CD163 (sCD163) are associated with the quantity of alcohol consumption. 148 subjects were enrolled (97 excessive drinkers (ED) and 51 controls). Time Line Follow-Back questionnaire was used to quantify the amount of alcohol consumed. Serum LPS, sCD14, and sCD163 were measured. Peripheral blood mononuclear cells (PBMCs) were also isolated. Compared to controls, ED had higher total drinks in the past 30 days, higher levels of LPS, sCD14 and sCD163. The levels of serum LPS, sCD14, and sCD163 were higher among ED with recent alcohol consumption (last drink 〈 10 days before enrollment) compared to those without recent drinking. Similar bacterial genome copy numbers were detected in control and ED groups. We found that ethanol primed PBMCs for LPS-induced inflammatory responses. A positive correlation between serum LPS, sCD14, sCD163 and the quantity of alcohol drinking was observed after adjusting for covariates and that abstinence was associated with decline in the levels of LPS, sCD14 and sCd163. We found an increase in the levels of LPS and markers of monocyte activations in ED. Further studies are needed to determine whether these can be used as the biomarkers for excessive alcohol use.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 2615211-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Infection and Immunity, American Society for Microbiology, Vol. 91, No. 3 ( 2023-03-15)
    Abstract: Many obligate intracellular bacteria, including members of the genus Chlamydia , cannot synthesize a variety of amino acids de novo and acquire these from host cells via largely unknown mechanisms. Previously, we determined that a missense mutation in ctl0225 , a conserved Chlamydia open reading frame of unknown function, mediated sensitivity to interferon gamma. Here, we show evidence that CTL0225 is a member of the SnatA family of neutral amino acid transporters that contributes to the import of several amino acids into Chlamydia cells. Further, we show that CTL0225 orthologs from two other distantly related obligate intracellular pathogens ( Coxiella burnetii and Buchnera aphidicola ) are sufficient to import valine into Escherichia coli . We also show that chlamydia infection and interferon exposure have opposing effects on amino acid metabolism, potentially explaining the relationship between CTL0225 and interferon sensitivity. Overall, we show that phylogenetically diverse intracellular pathogens use an ancient family of amino acid transporters to acquire host amino acids and provide another example of how nutritional virulence and immune evasion can be linked in obligate intracellular pathogens.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 1483247-1
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Online Resource
    Online Resource
    American Society for Microbiology ; 2012
    In:  Journal of Clinical Microbiology Vol. 50, No. 4 ( 2012-04), p. 1376-1383
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 50, No. 4 ( 2012-04), p. 1376-1383
    Abstract: Clinical urine specimens are usually considered to be sterile when they do not yield uropathogens using standard clinical cultivation procedures. Our aim was to test if the adult female bladder might contain bacteria that are not identified by these routine procedures. An additional aim was to identify and recommend the appropriate urine collection method for the study of bacterial communities in the female bladder. Consenting participants who were free of known urinary tract infection provided urine samples by voided, transurethral, and/or suprapubic collection methods. The presence of bacteria in these samples was assessed by bacterial culture, light microscopy, and 16S rRNA gene sequencing. Bacteria that are not or cannot be routinely cultivated (hereinafter called uncultivated bacteria) were common in voided urine, urine collected by transurethral catheter (TUC), and urine collected by suprapubic aspirate (SPA), regardless of whether the subjects had urinary symptoms. Voided urine samples contained mixtures of urinary and genital tract bacteria. Communities identified in parallel urine samples collected by TUC and SPA were similar. Uncultivated bacteria are clearly present in the bladders of some women. It remains unclear if these bacteria are viable and/or if their presence is relevant to idiopathic urinary tract conditions.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2012
    detail.hit.zdb_id: 1498353-9
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    In: Journal of Bacteriology, American Society for Microbiology, Vol. 198, No. 15 ( 2016-08), p. 2131-2139
    Abstract: Intracellular bacterial pathogens in the family Chlamydiaceae are causes of human blindness, sexually transmitted disease, and pneumonia. Genetic dissection of the mechanisms of chlamydial pathogenicity has been hindered by multiple limitations, including the inability to inactivate genes that would prevent the production of elementary bodies. Many genes are also Chlamydia -specific genes, and chlamydial genomes have undergone extensive reductive evolution, so functions often cannot be inferred from homologs in other organisms. Conditional mutants have been used to study essential genes of many microorganisms, so we screened a library of 4,184 ethyl methanesulfonate-mutagenized Chlamydia trachomatis isolates for temperature-sensitive (TS) mutants that developed normally at physiological temperature (37°C) but not at nonphysiological temperatures. Heat-sensitive TS mutants were identified at a high frequency, while cold-sensitive mutants were less common. Twelve TS mutants were mapped using a novel markerless recombination approach, PCR, and genome sequencing. TS alleles of genes that play essential roles in other bacteria and chlamydia-specific open reading frames (ORFs) of unknown function were identified. Temperature-shift assays determined that phenotypes of the mutants manifested at distinct points in the developmental cycle. Genome sequencing of a larger population of TS mutants also revealed that the screen had not reached saturation. In summary, we describe the first approach for studying essential chlamydial genes and broadly applicable strategies for genetic mapping in Chlamydia spp. and mutants that both define checkpoints and provide insights into the biology of the chlamydial developmental cycle. IMPORTANCE Study of the pathogenesis of Chlamydia spp. has historically been hampered by a lack of genetic tools. Although there has been recent progress in chlamydial genetics, the existing approaches have limitations for the study of the genes that mediate growth of these organisms in cell culture. We used a genetic screen to identify conditional Chlamydia mutants and then mapped these alleles using a broadly applicable recombination strategy. Phenotypes of the mutants provide fundamental insights into unexplored areas of chlamydial pathogenesis and intracellular biology. Finally, the reagents and approaches we describe are powerful resources for the investigation of these organisms.
    Type of Medium: Online Resource
    ISSN: 0021-9193 , 1098-5530
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1481988-0
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    In: BMC Microbiology, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1471-2180
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2041505-9
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Nursing Research Vol. 70, No. 4 ( 2021-7), p. 248-255
    In: Nursing Research, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. 4 ( 2021-7), p. 248-255
    Abstract: Dysmenorrhea is highly prevalent; it places women at risk for other chronic pain conditions. There is a high degree of individual variability in menstrual pain severity, the number of painful sites, and co-occurring gastrointestinal symptoms. Distinct dysmenorrhea symptom-based phenotypes were previously identified, but the biological underpinnings of these phenotypes are less known. One underexplored contributor is the vaginal microbiome. The vaginal microbiota differs significantly among reproductive-age women and may modulate as well as amplify reproductive tract inflammation, which may contribute to dysmenorrhea symptoms. Objectives The objective of this study was to examine associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome compositions on- and off-menses. Methods We conducted a prospective, longitudinal, pilot study of 20 women (aged 15–24 years) grouped into three dysmenorrhea symptom-based phenotypes: “mild localized pain,” “severe localized pain,” and “severe multiple pain and gastrointestinal symptoms.” Over one menstrual cycle, participants provided vaginal swabs when they were on- and off-menses. We assayed the vaginal microbiome using 16S rRNA gene sequencing. Permutational multivariate analysis of variance tests were used to compare microbiome compositions across phenotypes, with heat maps generated to visualize the relative abundance of bacterial taxa. Results The vaginal microbiome compositions ( n = 40) were different across the three phenotypes. After separating the on-menses ( n = 20) and off-menses ( n = 20) specimens, the statistically significant difference was seen on-menses, but not off-menses. Compared to the “mild localized pain” phenotype, participants in the “multiple severe symptoms” phenotype had a lower lactobacilli level and a higher abundance of Prevotella, Atopobium, and Gardnerella when on-menses. We also observed trends of differences across phenotypes in vaginal microbiome change from off- to on-menses. Discussion The study provides proof-of-concept data to support larger studies on associations between dysmenorrhea symptom-based phenotypes and vaginal microbiome that might lead to new intervention targets and/or biomarkers for dysmenorrhea. This line of research has the potential to inform precision dysmenorrhea treatment that can improve women’s quality of life.
    Type of Medium: Online Resource
    ISSN: 1538-9847 , 0029-6562
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1480527-3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2021
    In:  Journal of Clinical and Translational Science Vol. 5, No. s1 ( 2021-03), p. 87-88
    In: Journal of Clinical and Translational Science, Cambridge University Press (CUP), Vol. 5, No. s1 ( 2021-03), p. 87-88
    Abstract: ABSTRACT IMPACT: This project seeks to identify unique host responses that are biomarkers for specific urethral pathogens, and which can be used in the development of point-of-care (POC) STI diagnostics. OBJECTIVES/GOALS: How Chlamydia trachomatis (CT) and other common STIs, e.g. Neisseria gonorrhoeae, evade immunity and elicit pathology in the male urethra is poorly understood. Our objective is to determine how STI-infected urethral epithelial cells, as well as the uninfected ‘bystander’ cells with which infected cells communicate, respond to CT and other STIs. METHODS/STUDY POPULATION: We evaluated how immortalized urethral cell lines - including transduced human urethral epithelial cells (THUECs) - respond to increasing doses of CT infectious particles using in vitro one-step progeny assays performed in the presence or absence of cycloheximide, a drug that inhibits eukaryotic protein synthesis. We will perform concurrent single-cell RNA sequencing (scRNA-seq) and multiplex cytokine analyses to determine how different CT doses impact the transcriptomes of infected and bystander urethral epithelial cells and modulate cytokine production of the overall monolayer. Results of these experiments will inform the feasibility of performing similar analyses in situ using urethral swabs from men with clinically diagnosed urethritis. RESULTS/ANTICIPATED RESULTS: Our results demonstrate that immune-competent urethral cell monolayers strongly resist CT infection, unless most of the cells are simultaneously infected. This suggests that uninfected bystander cells sense CT-infected cells and secrete soluble factors that may act to limit CT proliferation in infected cells and to inform remaining uninfected cells that a potential pathogen is present. We anticipate that our scRNA-seq and cytokine analyses will identify both specific effector pathways that protect against CT and intracellular signals that modulate them. We speculate that these pathways and signals may differ during infection with CT and other STIs. Importantly, we anticipate that our in vitro model of CT infection will be highly representative of in situ immune responses observed in urethras of infected men. DISCUSSION/SIGNIFICANCE OF FINDINGS: In men, common STIs including CT are usually managed syndromically due to a lack of POC diagnostics. By determining how STIs elicit urethral inflammation and identifying countermeasures that STIs use to evade urethral immunity, we can identify host responses that serve as biomarkers for urethritis, generally, and for specific urethral pathogens.
    Type of Medium: Online Resource
    ISSN: 2059-8661
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2898186-8
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of Pediatric Gastroenterology & Nutrition Vol. 74, No. 5 ( 2022-05), p. e109-e114
    In: Journal of Pediatric Gastroenterology & Nutrition, Ovid Technologies (Wolters Kluwer Health), Vol. 74, No. 5 ( 2022-05), p. e109-e114
    Abstract: There is limited knowledge about the role of esophageal microbiome in pediatric esophageal eosinophilia (EE). We aimed to characterize the esophageal microbiome in pediatric patients with and without EE. Methods: In the present prospective study, esophageal mucosal biopsies were obtained from 41 children. Of these, 22 had normal esophageal mucosal biopsies (“healthy”), 6 children had reflux esophagitis (RE), 4 had proton pump inhibitor (PPi)-responsive esophageal eosinophilia (PPi-REE), and 9 had eosinophilic esophagitis (EoE). The microbiome composition was analyzed using 16S rRNA gene sequencing. The age median (range) in years for the healthy, RE, PPi-REE, and EoE group were 10 (1.5–18), 6 (2–15), 6.5 (5–15), and 9 (1.5–17), respectively. Results: The bacterial phylum Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria were the most predominant. The Epsilonproteobacteria, Betaproteobacteria, Flavobacteria, Fusobacteria, and Sphingobacteria class were underrepresented across groups. The Vibrionales was predominant in healthy and EoE group but lower in RE and PPi-REE groups. The genus Streptococcus, Rahnella, and Leptotrichia explained 29.65% of the variation in the data with an additional 10.86% variation in the data was explained by Microbacterium, Prevotella, and Vibrio genus. The healthy group had a higher diversity and richness index compared to other groups, but this was not statistically different. Conclusions: The pediatric esophagus has an abundant and diverse microbiome, both in the healthy and diseased states. The healthy group had a higher, but not significantly different, diversity and richness index compared to other groups.
    Type of Medium: Online Resource
    ISSN: 0277-2116 , 1536-4801
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 2078835-6
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: mBio, American Society for Microbiology, Vol. 11, No. 6 ( 2020-12-22)
    Abstract: Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum . Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease. IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.
    Type of Medium: Online Resource
    ISSN: 2161-2129 , 2150-7511
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 2557172-2
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages