• Comparative Metagenome-Assembled Genome Analysis of "Candidatus Lachnocurva vaginae", Formerly Known as Bacterial Vaginosis-Associated Bacterium?1 (BVAB1)

      Holm, J.B.; France, M.T.; Ma, B.; McComb, E.; Robinson, C.K.; Mehta, A.; Tallon, L.J.; Brotman, R.M.; Ravel, J. (Frontiers Media S.A., 2020)
      Bacterial vaginosis-associated bacterium 1 (BVAB1) is an as-yet uncultured bacterial species found in the human vagina that belongs to the family Lachnospiraceae within the order Clostridiales. As its name suggests, this bacterium is often associated with bacterial vaginosis (BV), a common vaginal disorder that has been shown to increase a woman's risk for HIV, Chlamydia trachomatis, and Neisseria gonorrhoeae infections as well as preterm birth. BVAB1 has been further associated with the persistence of BV following metronidazole treatment, increased vaginal inflammation, and adverse obstetrics outcomes. There is no available complete genome sequence of BVAB1, which has made it difficult to mechanistically understand its role in disease. We present here a circularized metagenome-assembled genome (cMAG) of BVAB1 as well as a comparative analysis including an additional six metagenome-assembled genomes (MAGs) of this species. These sequences were derived from cervicovaginal samples of seven separate women. The cMAG was obtained from a metagenome sequenced with long-read technology on a PacBio Sequel II instrument while the others were derived from metagenomes sequenced on the Illumina HiSeq platform. The cMAG is 1.649 Mb in size and encodes 1,578 genes. We propose to rename BVAB1 to "Candidatus Lachnocurva vaginae" based on phylogenetic analyses, and provide genomic and metabolomic evidence that this candidate species may metabolize D-lactate, produce trimethylamine (one of the chemicals responsible for BV-associated odor), and be motile. The cMAG and the six MAGs are valuable resources that will further contribute to our understanding of the heterogeneous etiology of bacterial vaginosis. Copyright 2020 The Authors.
    • Complete Genome Sequence of Lactobacillus crispatus CO3MRSI1

      McComb, E.; Holm, J.; Ma, B. (American Society for Microbiology, 2019)
      Lactobacillus crispatus is a commonly found bacterium in vertebrate microbiota, particularly the human vagina. We report the first complete genome of a strain isolated from a human vagina, L. crispatus CO3MRSI1. © 2019 McComb et al.
    • Complete genome sequences of six lactobacillus iners strains isolated from the human vagina

      France, M.T.; Rutt, L.; Narina, S.; Arbaugh, S.; McComb, E.; Humphrys, M.S.; Ma, B.; Ravel, J. (American Society for Microbiology, 2020)
      Lactobacillus iners is a common member of the human vaginal microbiota, with a genome size smaller than that of other lactobacilli. Here, we report the complete genome sequences of six L. iners strains isolated from different vaginal swab specimens. Three strains were found to harbor ∼100-kbp plasmids, which were not known previously. Copyright 2020 France et al.
    • A comprehensive non-redundant gene catalog reveals extensive within-community intraspecies diversity in the human vagina

      Ma, B.; France, M.T.; Crabtree, J.; Holm, J.B.; Humphrys, M.S.; Brotman, R.M.; Ravel, J. (Nature Research, 2020)
      Analysis of metagenomic and metatranscriptomic data is complicated and typically requires extensive computational resources. Leveraging a curated reference database of genes encoded by members of the target microbiome can make these analyses more tractable. In this study, we assemble a comprehensive human vaginal non-redundant gene catalog (VIRGO) that includes 0.95 million non-redundant genes. The gene catalog is functionally and taxonomically annotated. We also construct a vaginal orthologous groups (VOG) from VIRGO. The gene-centric design of VIRGO and VOG provides an easily accessible tool to comprehensively characterize the structure and function of vaginal metagenome and metatranscriptome datasets. To highlight the utility of VIRGO, we analyze 1,507 additional vaginal metagenomes, and identify a high degree of intraspecies diversity within and across vaginal microbiota. VIRGO offers a convenient reference database and toolkit that will facilitate a more in-depth understanding of the role of vaginal microorganisms in women's health and reproductive outcomes. Copyright 2020, The Author(s).
    • Host-targeted niclosamide inhibits C. difficile virulence and prevents disease in mice without disrupting the gut microbiota

      Tam, J.; Hamza, T.; Ma, B. (Nature Publishing Group, 2018)
      Clostridium difficile is the leading cause of nosocomial diarrhea and colitis in the industrialized world. Disruption of the protective gut microbiota by antibiotics enables colonization by multidrug-resistant C. difficile, which secrete up to three different protein toxins that are responsible for the gastrointestinal sequelae. Oral agents that inhibit the damage induced by toxins, without altering the gut microbiota, are urgently needed to prevent primary disease and break the cycle of antibiotic-induced disease recurrence. Here, we show that the anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for entry into colonocytes by each toxin. In mice infected with an epidemic strain of C. difficile, expressing all three toxins, niclosamide reduced both primary disease and recurrence, without disrupting the diversity or composition of the gut microbiota. Given its excellent safety profile, niclosamide may address an important unmet need in preventing C. difficile primary and recurrent diseases. Copyright 2018, The Author(s).
    • Microbial biomarkers of intestinal barrier maturation in preterm infants

      Ma, B.; McComb, E.; Gajer, P. (Frontiers Media S.A., 2018)
      Intestinal barrier immaturity, or "leaky gut," is the proximate cause of susceptibility to necrotizing enterocolitis in preterm neonates. However, the impact of intestinal microbiota development on intestinal mucosal barrier maturation has not been evaluated in this population. In this study, we investigated a longitudinally sampled cohort of 38 preterm infants < 33 weeks gestation monitored for intestinal permeability (IP) and fecal microbiota during the first 2 weeks of life. Rapid decrease in IP indicating intestinal barrier function maturation correlated with significant increase in community diversity. In particular, members of the Clostridiales and Bifidobacterium were highly transcriptionally active, and progressively increasing abundance in Clostridiales was significantly associated with decreased intestinal permeability. Further, neonatal factors previously identified to promote intestinal barrier maturation, including early exclusive breastmilk feeding and shorter duration antibiotic exposure, associate with the early colonization of the intestinal microbiota by members of the Clostridiales, which altogether are associated with improved intestinal barrier function in preterm infants. Copyright Copyright 2018 Ma, McComb, Gajer, Yang, Humphrys, Okogbule-Wonodi, Fasano, Ravel and Viscardi.
    • Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia trachomatis Infection

      Gajer, P.; Humphrys, M.S.; Terplan, M.; Mark, K.S.; Brotman, R.M.; Bavoil, P.M.; Ravel, J.; Ma, B. (Oxford University Press, 2020)
      We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis-associated bacteria including Gardnerella vaginalis. Interestingly, L. iners-dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus iners-dominated communities have been associated with increased risk of C. trachomatis infection, suggesting that the impact of antibiotic treatment on the vaginal microbiota could favor reinfections. These results provide support for the dual need to account for the potential perturbing effect(s) of antibiotic treatment on the vaginal microbiota, and to develop strategies to protect and restore optimal vaginal microbiota. Copyright The Author(s) 2019.
    • Vaginal Candida spp. genomes from women with vulvovaginal candidiasis

      Bradford, L.L.; Chibucos, M.C.; Ma, B. (Oxford University Press, 2017)
      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.