Strain-level variation among vaginal Lactobacillus crispatus and Lactobacillus iners as identified by comparative metagenomics

The vaginal microbiome, a relatively simple, low diversity ecosystem crucial for female health, is often dominated by Lactobacillus spp. Detailed strain-level data, facilitated by shotgun sequencing, can provide a greater understanding of the mechanisms of colonization and host-microbe interactions. We analysed 354 vaginal metagenomes from pregnant women in Ireland to investigate metagenomic community state types and strain-level variation, focusing on cell surface interfaces. Our analysis revealed multiple subspecies, with Lactobacillus crispatus and Lactobacillus iners being the most dominant. We found genes, including putative mucin-binding genes, distinct to L. crispatus subspecies. Using 337 metagenome-assembled genomes, we observed a higher number of strain-specific genes in L. crispatus related to cell wall biogenesis, carbohydrate and amino acid metabolism, many under positive selection. A cell surface glycan gene cluster was predominantly found in L. crispatus but absent in L. iners and Gardnerella vaginalis. These findings highlight strain-specific factors associated with colonisation and host-microbe interactions.