Objectives Some vaginal bacterial communities are thought to prevent infection by sexually transmitted organisms. Prior work demonstrated that the vaginal microbiota of reproductive-age women cluster into five types of bacterial communities; 4 dominated by Lactobacillus species (L. iners, L. crispatus, L. gasseri, L. jensenii), and one (termed community state type (CST) IV) lacking significant numbers of lactobacilli and characterized by higher proportions of Atopobium, Prevotella, Parvimonas, Sneathia, Gardnerella, Mobiluncus, and other taxa. We sought to evaluate the relationship between vaginal bacterial composition and Trichomonas vaginalis. Methods Self-collected vaginal swabs were obtained cross-sectionally from 394 women equally representing four ethnic/racial groups. T. vaginalis screening was performed using PCR targeting the 18S rRNA and β-tubulin genes. Vaginal bacterial composition was characterized by pyrosequencing of barcoded 16S rRNA genes. A panel of eleven microsatellite markers was used to genotype T. vaginalis. The association between vaginal microbiota and T. vaginalis was evaluated by exact logistic regression. Results T. vaginalis was detected in 2.8% of participants (11/394). Of the eleven T. vaginalis-positive cases, eight (72%) were categorized as CST-IV, two (18%) as communities dominated by L. iners and one (9%) as L. crispatus-dominated (p-value:0.05). CST-IV microbiota were associated with an 8-fold increased odds of detecting T. vaginalis compared to women in the L. crispatus-dominated state (OR:8.26, 95% CI:1.07–372.65). Seven of the 11 T. vaginalis isolates were assigned to two genotypes. Conclusion T. vaginalis was associated with vaginal microbiota consisting of low proportions of lactobacilli and high proportions of Mycoplasma, Parvimonas, Sneathia, and other anaerobes.

Most of what is known about fungi in the human vagina has come from culture-based studies and phenotypic characterization of single organisms. Though valuable, these approaches have masked the complexity of fungal communities within the vagina. The vaginal mycobiome has become an emerging field of study as genomics tools are increasingly employed and we begin to appreciate the role these fungal communities play in human health and disease. Though vastly outnumbered by its bacterial counterparts, fungi are important constituents of the vaginal ecosystem in many healthy women. Candida albicans, an opportunistic fungal pathogen, colonizes 20% of women without causing any overt symptoms, yet it is one of the leading causes of infectious vaginitis. Understanding its mechanisms of commensalism and pathogenesis are both essential to developing more effective therapies. Describing the interactions between Candida, bacteria (such as Lactobacillus spp.) and other fungi in the vagina is fundamental to our characterization of the vaginal mycobiome.

Candida albicans, the major invasive fungal pathogen of humans, can cause both debilitating mucosal infections and fatal invasive infections. Understanding the complex nature of the host-pathogen interaction in each of these contexts is essential to developing desperately needed therapies to treat fungal infections. RNA-seq enables a systems-level understanding of infection by facilitating comprehensive analysis of transcriptomes from multiple species (e.g., host and pathogen) simultaneously. We used RNA-seq to characterize the transcriptomes of both C. albicans and human endothelial cells or oral epithelial cells during in vitro infection. Network analysis of the differentially expressed genes identified the activation of several signaling pathways that have not previously been associated with the host response to fungal pathogens. Using an siRNA knockdown approach, we demonstrate that two of these pathways-platelet-derived growth factor BB (PDGF BB) and neural precursor-cell-expressed developmentally down-regulated protein 9 (NEDD9)-govern the host-pathogen interaction by regulating the uptake of C. albicans by host cells. Using RNA-seq analysis of a mouse model of hematogenously disseminated candidiasis (HDC) and episodes of vulvovaginal candidiasis (VVC) in humans, we found evidence that many of the same signaling pathways are activated during mucosal (VVC) and/or disseminated (HDC) infections in vivo. Our analyses have uncovered several signaling pathways at the interface between C. albicans and host cells in various contexts of infection, and suggest that PDGF BB and NEDD9 play important roles in this interaction. In addition, these data provide a valuable community resource for better understanding host-fungal pathogen interactions.

Background Vulvovaginal candidiasis is commonly diagnosed and has been associated in prospective studies with the acquisition of HIV. Little data is available on how the composition of the vaginal microbiota, and other risk factors, are associated with the molecular detection of Candida albicans—a common cause of vulvovaginal candidiasis. Methods In a cross-sectional study, self-collected vaginal swabs were obtained from 394 nonpregnant, reproductive-age women. C. albicans was detected using polymerase chain reaction targeting C. albicans ITS1/2 region. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing of the V3 to V4 hypervariable regions and clustered into community state types (CSTs). Multiple logistic regression identified factors associated with C. albicans detection. Results Twenty-one percent had C. albicans detected and 46% reported vaginal symptoms in the prior 60 days. There was a 2-fold increase in the odds of C. albicans if a woman was in a L. crispatus-dominated CST compared to CSTs with low-Lactobacillus levels (adjusted odds ratio, 2.05; 95% confidence interval, 0.97–4.37). History of self-treatment with antifungals, L. crispatus relative abundance, and receptive oral sex were also significantly associated with C. albicans detection. Conclusions A L. crispatus-dominated vaginal microbiota is thought to protect women from both development of bacterial vaginosis and incidence of sexually transmitted infections; however, our data suggest that L. crispatus is associated with increased C. albicans detection. Receptive oral sex may also be a risk factor for vaginal C. albicans colonization.

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Candida albicans is the predominant cause of vulvovaginal candidiasis (VVC). Little is known regarding the genetic diversity of Candida spp. in the vagina or the microvariations in strains over time that may contribute to the development of VVC. This study reports the draft genome sequences of four C. albicans and one C. glabrata strains isolated from women with VVC. An SNP-based whole-genome phylogeny indicates that these isolates are closely related; however, phylogenetic distances between them suggest that there may be genetic adaptations driven by unique host environments. These sequences will facilitate further comparative analyses and ultimately improve our understanding of genetic variation in isolates of Candida spp. that are associated with VVC.

Neonatal sepsis is a significant cause of morbidity and mortality among term and preterm infants. Ampicillin and gentamicin are standard empiric therapy for early onset sepsis. Four cases of neonatal sepsis secondary to Escherichia coli (E. coli) found to be gentamicin resistant occurred within a five week period in one neonatal intensive care unit (NICU). To determine whether these cases could be tied to a single vector of transmission, and to more broadly evaluate the incidence of gentamicin resistant strains of E. coli in the neonatal population at our institution compared to other centers, we reviewed the charts of the four neonates (Infants A through D) and their mothers. The E. coli isolates were sent for Pulse Field Gel Electrophoresis (PFGE) to evaluate for genetic similarity between strains. We also reviewed all positive E. coli cultures from one NICU over a two year period. Infants A and B had genetically indistinguishable strains which matched that of urine and placental cultures of Infant B's mother. Infant C had a genetically distinct organism. Infant D, the identical twin of Infant C, did not have typing performed. Review of all cultures positive for E. coli at our institution showed a 12.9 percent incidence of gentamicin-resistance. A review of other studies showed that rates of resistance vary considerably by institution. We conclude that gentamicin-resistant E. coli is a relatively uncommon cause of neonatal sepsis, but should remain a consideration in patients who deteriorate despite initiation of empiric antibiotics.