Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis.

Anna-Ursula Happel,Shaun L Barnabas,Smritee Dabee,Glenda Gray,Brian Kullin,Heather B Jaspan,Jo-Ann S Passmore,Hoyam Gamieldien,Shameem Z Jaumdally,Linda-Gail Bekker,Remy Froissart,Chambrez Z Zauchenberger,Janan Dietrich,Nicole Wentzel

doi:10.1371/journal.ppat.1008559

Abstract

Antibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract. Characteristics of vaginal Lactobacillus strains from South African women were evaluated for their probiotic potential in vitro compared to strains from commercial vaginal products, including growth at varying pHs, ability to lower pH, produce D-/L-lactate and H2O2, influence growth of BV-associated Gardnerella vaginalis and Prevotella bivia, adherence to cervical cells and susceptibility to antibiotics. Fifty-seven Lactobacillus strains were purified from cervico-vaginal fluid, including L. crispatus, L. jensenii, L. gasseri, L. mucosae, and L. vaginalis. L crispatus strains grew better at pHs below 4.5 and lowered pH more effectively than other strains. Production of D-/L-lactate and H2O2 varied between Lactobacillus species and strains. Lactobacillus strains generally inhibited P. bivia more uniformly than G. vaginalis isolates. All vaginal Lactobacillus isolates were resistant to metronidazole while susceptibility to clindamycin varied. Furthermore, vaginal Lactobacillus strains tended to be broadly susceptible to penicillin, amoxicillin, rifampicin and rifabutin. Whole-genome-sequencing of five of the best-performing vaginal Lactobacillus strains confirmed their likely safety, due to antimicrobial resistance elements being largely absent, while putative intact prophages were present in the genomes of two of the five strains. Overall, vaginal Lactobacillus strains largely performed better in these in vitro assays than probiotic strains currently used in probiotics for vaginal health. Including the best-performing vaginal Lactobacillus isolates in a region-specific probiotic for vaginal health may result in improved BV treatment options.

Highlights

Maintenance of vaginal health is important in protecting women from adverse urogenital and reproductive health outcomes [1]
Bacterial vaginosis is associated with adverse pregnancy outcomes and increased risk of sexually transmitted infections, including human immunodeficiency virus (HIV)
We characterised a large panel of vaginal Lactobacillus strains from young African women, compared to isolates from commercial probiotic products for vaginal health

Summary

Introduction

Maintenance of vaginal health is important in protecting women from adverse urogenital and reproductive health outcomes [1]. As a result of this, several clinical studies evaluated Lactobacillus-containing probiotics as an adjunct to BV treatment and have shown largely beneficial heterogeneous outcomes [14,15,16,17]. We evaluated a range of PPP characteristics that should be considered in the development of vaginal probiotics. These included: (1) originating from the FGT, as vaginal Lactobacillus spp. are highly adapted for this specialized niche [19]; (2) ability to adhere well to FGT cells, as adherent isolates are more likely to remain locally [20,21,22]; (3) inhibiting the growth of BV-associated species, including

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