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The pathogenesis of mycoplasmas requires their attachment to the epithelial mucosa membrane of the host cells, followed by colonisation and necrotic destruction of the submucosal tissue. The extent of this pathogenesis depends on the ability of species of Mycoplasma to effectively attach and invade the host's tissue. In this regard, the cytadherence tip organelle has evolved within the mycoplasmas to accomplish this feat. However, species of Mycoplasma that do not possess the specialized structure remain virulent with the use of surface-membrane lipoproteins. The lipoprotein ligands bind to sulfatides and sialoglycoconjugates on the host's mucosa membranes. This hostmycoplasma interaction, though poorly studied, appears to have a wide underlying array of complex molecular mechanisms, which after activation trigger cytadherence, immunomodulation and virulence. Mycoplasmas with their highly redundant minimal genomes display dynamic genotypic and phenotypic plasticity; a trait that has allowed them to adapt, persist and survive successfully in adverse niches through circumvention and tempering of the host's humoral immune response. Additionally, the linkages between the mycoplasmas persistence and chronic inflammatory diseases in humans necessitate examining the host-mycoplasma interaction at the proteogenomic level. This paper provides an overview on the molecular mechanisms involved in cytadherence, surfacemembrane antigenic variation and survival strategies of human urogenital mycoplasmas.

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Background Intra-continentally, vaginal microbiome signatures are reported to be significantly different between Black and Caucasian women, with women of African ancestry having the less well defined heterogenous bacterial community state type (CST) deficient of Lactobacillus species (CST IV). The objective of this study was to characterize the vaginal microbiomes across a more diverse intercontinental group of women (N = 151) of different ethnicities (African American, African Kenyan, Afro-Caribbean, Asian Indonesian and Caucasian German) using 16S rRNA gene sequence analysis to determine their structures and offer a comprehensive description of the non-Lactobacillus dominant CSTs and subtypes. Results In this study, the bacterial composition of the vaginal microbiomes differed significantly among the ethnic groups. Lactobacillus spp. (L. crispatus and L. iners) dominated the vaginal microbiomes in African American women (91.8%) compared to European (German, 42.4%), Asian (Indonesian, 45.0%), African (Kenyan, 34.4%) and Afro-Caribbean (26.1%) women. Expanding on CST classification, three subtypes of CST IV (CST IV-A, IV-B and IV-C) (N = 56, 37.1%) and four additional CSTs were described: CST VI Gardnerella vaginalis—dominant (N = 6, 21.8%); CST VII (Prevotella—dominant, N = 1, 0.66%); CST VIII (N = 9, 5.96%), resembling aerobic vaginitis, was differentiated by a high proportion of taxa such as Enterococcus, Streptococcus and Staphylococcus (relative abundance [RA] > 50%) and CST IX (N = 7, 4.64%) dominated by genera other than Lactobacillus, Gardnerella or Prevotella (e.g., Bifidobacterium breve and Anaerococcus vaginalis). Within the vaginal microbiomes, 32 “taxa with high pathogenic potential” (THPP) were identified. Collectively, THPP (mean RA ~5.24%) negatively correlated (rs = −0.68, p < 2.2e−16) with Lactobacillus species but not significantly with Gardnerella/Prevotella spp. combined (r = −0.13, p = 0.1). However, at the individual level, Mycoplasma hominis exhibited moderate positive correlations with Gardnerella (r = 0.46, p = 2.6e−09) and Prevotella spp. (r = 0.47, p = 1.4e−09). Conclusions These findings while supporting the idea that vaginal microbiomes vary with ethnicity, also suggest that CSTs are more wide-ranging and not exclusive to any particular ethnic group. This study offers additional insight into the structure of the vaginal microbiome and contributes to the description and subcategorization of non-Lactobacillus-dominated CSTs.

Background The cervicovaginal microbiome, with its well documented dynamic community state types (CSTs I-V) is known to interact with the host immune system in a complex regulatory ecosystem that guards against dysbiosis and invading pathogens. However, the regulatory mechanism of the cervicovaginal microbiome in vaginal eubiosis is not well understood. Therefore, we characterized the cervicovaginal microbiome in a cohort of Afro-Caribbean women to the species-strain taxonomic level using high-throughput targeted sequencing and shotgun metagenomics and conceptualized a hypothetical model that aids in understanding vaginal ecosystem regulation. Results Compared to targeted 16S rRNA V4 sequencing, whole genome shotgun (WGS) metagenomics offered greater species resolution of the cervicovaginal microbiome in the Afro-Caribbean women cohort. Community state type IV predominated in the microbiome of these women, with Prevotella (13.91%), Gardnerella (12.14%) and Lactobacillus (9.37%) being the three most abundant genera. For Prevotella and Lactobacillus the most abundant species-strains were P. timonensis DSM 22865 (5.0%) and L. iners DSM 13335 (7.0%), respectively. The less virulent strain of Gardnerella, G. vaginalis 409-05 (8.0%) was more abundant than G. vaginalis ATCC 14019 (4.0%). In the resistome, 2,753 antimicrobial resistance (AMR) genes consisting of 28 types (mostly tet and Emr; abundances 51% and 15%, respectively) which confer resistance to tetracyclines and the macrolide-lincosamide streptogramin B (MLSb phenotype) group were observed. Functional profiling showed a high abundance of biological processes (bacterial-type flagellum-dependent cell motility, cell adhesion, response to biotic stimulus and quorum sensing) associated with biofilm activity. Conclusions Characterized for the first time, the cervicovaginal microbiome in Afro-Caribbean women is predominantly CST IV with the three most abundant taxa consisting of bacterial strains P. timonensis DSM 22865, G. vaginalis 409-05 and L. iners DSM 13335. Its resistome had multiple AMR genes that confer resistance to antibiotics commonly used in the treatment of sexually transmitted infections (STIs) and bacterial vaginosis (BV). In this study, the occurrence of biofilm activity within the cervicovaginal microbiome suggested a possible regulatory role. We present a conceptual immuno-munibiome model that advances a mechanistic approach for the structure and regulation of the vaginal ecosystem in the Afro-Caribbean women cohort.

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