Abstract
The interaction between gut bacterial and viral microbiota is thought to be important in human health. While fluctuations in female genital tract (FGT) bacterial microbiota similarly determine sexual health, little is known about the presence, persistence, and function of vaginal bacteriophages. We conducted shotgun metagenome sequencing of cervicovaginal samples from South African adolescents collected longitudinally, who received no antibiotics. We annotated viral reads and circular bacteriophages, identified CRISPR loci and putative prophages, and assessed their diversity, persistence, and associations with bacterial microbiota composition. Siphoviridae was the most prevalent bacteriophage family, followed by Myoviridae, Podoviridae, Herelleviridae, and Inoviridae. Full-length siphoviruses targeting bacterial vaginosis (BV)-associated bacteria were identified, suggesting their presence in vivo. CRISPR loci and prophage-like elements were common, and genomic analysis suggested higher diversity among Gardnerella than Lactobacillus prophages. We found that some prophages were highly persistent within participants, and identical prophages were present in cervicovaginal secretions of multiple participants, suggesting that prophages, and thus bacterial strains, are shared between adolescents. The number of CRISPR loci and prophages were associated with vaginal microbiota stability and absence of BV. Our analysis suggests that (pro)phages are common in the FGT and vaginal bacteria and (pro)phages may interact.
Highlights
Bacteriophages are one of the most abundant and diverse biological entities on earth, and they play an important role in shaping the structure of bacterial communities and in contributing to the evolution of bacterial genomes [1,2,3]
Status throughout the study period. This suggests a high persistence of prophages over time in the female genital tract (FGT), unless vaginal microbiota composition changed between visits. These results further suggest that the presence of prophages within the genomes of vaginal bacteria may contribute to the stability of the vaginal microbiota, as it has been previously shown that occurrence of prophages within bacterial genomes can provide fitness benefits [20,21,22,23,24,25] and protection against secondary bacteriophage infection [26,27,28], both of which might allow host bacterial persistence and avoid disruption of the vaginal microbiota
We found that prophages integrated in predominant FGT bacterial taxa were highly persistent in the cervicovaginal secretions of a given participant over time
Summary
Bacteriophages are one of the most abundant and diverse biological entities on earth, and they play an important role in shaping the structure of bacterial communities and in contributing to the evolution of bacterial genomes [1,2,3]. Diversity and dynamics of bacteriophage community composition have been associated with various adverse health outcomes in humans, including the ability of opportunistic bacterial pathogens to establish in the gut [4,5], pathogenesis of inflammatory bowel disease [6,7,8], immunodeficiency in human immunodeficiency virus (HIV) disease [9], and severity of respiratory tract infections [10]. Both direct and indirect ecological interactions have been proposed to contribute to these outcomes. Cryptic prophages modulate genetic diversity and functionality of bacterial communities [3,19]
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