Project description:Staphylococcus aureus has emerged as a significant pathogen causing severe, invasive disease in otherwise healthy people. Despite considerable advances in understanding the epidemiology, resistance mechanisms, and virulence factors produced by the bacteria, there is limited knowledge of the in vivo host immune response to acute, invasive S. aureus infections. Herein, we report that peripheral blood mononuclear cells from patients with severe S. aureus infections demonstrate a distinctive and robust gene expression profile which is validated in a distinct group of patients and on a different microarray platform. Application of a systems-wide modular analysis framework reveals significant over-expression of innate immunity genes and under-expression of genes related to adaptive immunity. Simultaneous flow cytometry analyses demonstrated marked alterations in immune cell numbers, with decreased central memory CD4 and CD8 T cells and increased number of monocytes. CD14+ monocyte numbers significantly correlated with the gene expression levels of genes related to the innate immune response. These results demonstrate the value of applying a systems biology approach that reveals the significant alterations in the components of circulating blood lymphocytes and monocytes in invasive S. aureus infections.
Project description:<p>Urethral microbiome of adolescent males is designed to characterize the microbial communities resident in the urethra of young men, to identify differences in these communities as a function of race/ethnicity, circumcision status, sexual exposures, and uro-genital symptoms. We collect detailed sexual behavior and symptoms data using cellular telephones with Internet access. Specimens are routinely collected at monthly intervals, and intermittently following reported symptoms, specific sexual exposures, or identification of a sexually transmitted infection. We also collect periodic samples from the penile coronal sulcus to better characterize its relationship to the urethral micriobial communities.</p> <p>Participants are ages 14 - 17 at enrollment, and prior history of sexual exposure is not required for participation. Parental permission is obtained for each participant. The planned duration of followup is up to 4 years allowing for prospective observation of both physical and behavioral maturation from middle adolescence into young adulthood.</p> <p>The overall objectives of the project are to better characterize the healthy male urethral microbiome, and to use this information to better understand acquisition of urethritis and sexually transmitted infections, as well as chronic genital pain and prostatitis syndromes that become common among young adults.</p>
| phs000259 | dbGaP
Project description:Doxycycline post-exposure prophylaxis for sexually transmitted infections impacts the gut antimicrobial resistome
Project description:Introduction: Structural integrity of the cervical epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections, including HIV. Female sex hormones, estradiol and progesterone, play an important role in modulating this epithelial barrier. However, the influence of fluctuating estradiol and progesterone on ectocervical tissue gene and protein expression in naturally cycling women at high risk for sexually transmitted infections is not well understood. Methods: Ectocervical biopsies, cervicovaginal lavage fluid, and venous blood samples were collected from naturally cycling Kenyan female sex workers at two time points, separated by 2 weeks. The first time point represented the luteal phase of the menstrual cycle and the second time point represented the follicular phase. Plasma estradiol and progesterone levels were measured at each time point. Ectocervical tissues were analyzed by RNA-sequencing and in situ immunofluorescence staining. Cervicovaginal lavage samples were evaluated using antibody-based protein profiling. Results: Employing a systems biology approach, we demonstrated that high plasma estradiol levels enhanced ectocervical epithelial integrity. These findings were more pronounced in samples from the follicular phase (when progesterone and estradiol levels were significantly lower) and included increased expression, and more intact distribution, of the desmosomal cadherin DSG1. The effects of progesterone on gene and protein levels, as well as on intact tissue (as visualized by in situ staining), were modest throughout the menstrual cycle. Both estradiol and progesterone levels had limited influence on mucosal immune factors. Conclusion: Estradiol levels were associated with modulation of cervical epithelial barrier integrity, including the expression and distribution of DSG1, during the follicular phase of natural menstrual cycles in Kenyan sex workers.
Project description:Because zika virus is sexually transmitted, with sought to investigate how ZIKV infection affect the transcriptome of sertoli cells, which are nurse cells
Project description:Chlamydia trachomatis (C. trachomatis) is an intracellular bacterium, and is one of the main pathogens that cause sexually transmitted infections worldwide. Long non-coding RNAs (lncRNAs) have become vital regulators in many biological processes. However, few studies have shown that lncRNAs take part in the pathogenesis of C. trachomatis. Here, we used microarrays to study the expression profiles of lncRNAs and mRNAs in HeLa cells at 12, 24, and 40 hours pot-infection (hpi). Our study provides evidence that lncRNAs are involved in the interaction between C. trachomatis and hosts.
Project description:The sexually transmitted parasite Trichomonas vaginalis secretes extracellular vesicles (TvEVs) that are internalized by human host cells. The goal of this experiment was to identify the effects of TvEV uptake on host cell gene expression.
Project description:BACKGROUND: Infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging worldwide. We investigated an outbreak of severe CA-MRSA infections in children following out-patient vaccination. METHODS AND FINDINGS: We carried out a field investigation after adverse events following immunization (AEFI) were reported. We reviewed the clinical data from all cases. S. aureus recovered from skin infections and from nasal and throat swabs were analyzed by pulse-field gel electrophoresis, multi locus sequence typing, PCR and microarray. In May 2006, nine children presented with AEFI, ranging from fatal toxic shock syndrome, necrotizing soft tissue infection, purulent abscesses, to fever with rash. All had received a vaccination injection in different health centres in one District of Ho Chi Minh City. Eight children had been vaccinated by the same health care worker (HCW). Deficiencies in vaccine quality, storage practices, or preparation and delivery were not found. Infection control practices were insufficient. CA-MRSA was cultured in four children and from nasal and throat swabs from the HCW. Strains from children and HCW were indistinguishable. All carried the Panton-Valentine leukocidine (PVL), the staphylococcal enterotoxin B gene, the gene complex for staphylococcal-cassette-chromosome mec type V, and were sequence type 59. Strain HCM3A is epidemiologically unrelated to a strain of ST59 prevalent in the USA, although they belong to the same lineage. CONCLUSIONS: We describe an outbreak of infections with CA-MRSA in children, transmitted by an asymptomatic colonized HCW during immunization injection. Consistent adherence to injection practice guidelines is needed to prevent CA-MRSA transmission in both in- and outpatient settings. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-45
Project description:Purpose: The goal of this study was to compare gene expression patterns in the male and female human cortex Methods: We performed RiboZero Gold (rRNA depleted) 50bp PE RNA-seq in a set of control samples of both sexes to identify sexually dimorphic gene expression patterns. Results: Within these samples, we corroborated findings from a discovery set of RNA-seq data from adult human cortex tissue from the BrainSpan consortium which demonstrated male-biased expression of astrocyte marker genes and a gene co-expression module found to be up-regulated in the adult autistic cortex. Conclusions: These findings suggest that sex-differential risk for autism spectrum disorder is not the result of sex-differential regulation of ASD risk genes, but of naturally occurring sexually dimorphic processes that modulate the impact of risk variants for autism spectrum disorder. 13 cerebral cortex samples from 10 individuals (7 samples from 5 males, 6 samples from 5 females). Three Samples are included in this study from Series GSE64018. **PLEASE NOTE: Raw data has been submitted to dbGAP**