Characterisation of vaginal Lactobacillus isolates from South African women towards the development of a biotherapeutic to optimise the vaginal microbiome

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Abstract HIV remains among the world’s most serious healthcare challenges, with adolescent girls and young women in sub-Saharan Africa at particularly high risk of infection. Bacterial vaginosis (BV) is a key risk factor for HIV acquisition, however current treatment strategies are limited. Optimal vaginal Lactobacillus spp. protect against BV and HIV, largely through immunoregulatory and antimicrobial activities mediated in part by lactic acid. Towards the development of a Lactobacillus -containing live biotherapeutic for African women, we sampled 181 vaginal Lactobacillus isolates from 25 BV-negative South African women. Fifty isolates were selected for evaluation of inflammatory responses using vaginal epithelial cells, D- and L-lactate and lactic acid production and culture acidification. Aside from a single Lactobacillus salivarius strain, L. crispatus isolates acidified the culture media the most and produced the most D- and L-lactic acid. Inflammatory cytokine responses to Lactobacillus strains were variable, with L. crispatus eliciting the lowest levels of cytokine production. When all properties were evaluated collectively, L. crispatus strains exhibited the most desirable biotherapeutic characteristics. Whole genome sequence analysis of ten L. crispatus isolates showed that the majority were more closely related to one another than to isolates from other geographical regions. This supports the need for live biotherapeutics to be tailored for the population of intended use. No antimicrobial resistance elements were detected, while putative bacteriocins and intact prophage sequences were identified in all isolates. L. crispatus isolates displayed characteristics essential for optimal live biotherapeutic performance, however additional analysis is required to determine the functionality of identified putative prophages. Importance HIV is a leading cause of morbidity and mortality in sub-Saharan Africa, where adolescent girls and young women are three times more likely to acquire HIV than their male counterparts. A key risk factor for HIV is bacterial vaginosis (BV), a condition characterised by the loss of beneficial Lactobacillus species and increased abundance of non-optimal, inflammatory bacteria. Although BV affects approximately 25% of women in sub-Saharan Africa, effective therapeutics are lacking. Live biotherapeutics containing optimal Lactobacillus spp. represent a promising strategy to improve BV treatment outcomes and reduce HIV infection risk. We isolated 181 vaginal Lactobacillus spp. from 25 BV-negative South African women and characterized 50 selected isolates. This led to the identification of live biotherapeutic candidates for African women with distinct genomes compared to isolates from other geographical regions. This study contributes to current knowledge of the characteristics that should be considered when screening novel isolates for this purpose.

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