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

PLOS PATHOGENS(2020)

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摘要
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. Author summaryLactobacillus species in the lower reproductive tract of healthy women lower vaginal pH and protect against sexually transmitted infections. However, women commonly suffer from bacterial vaginosis, a disruption in the optimal Lactobacillus-dominated genital microbiota to a more diverse one marked by higher pH, vaginal discharge and inflammation. Bacterial vaginosis is associated with adverse pregnancy outcomes and increased risk of sexually transmitted infections, including HIV. While antibiotics are the standard-of-care for bacterial vaginosis, most cases recur within six-months. Probiotics that include lactobacilli have been explored to improve treatment, although the majority of products do not contain species commonly found in the vagina. Here, we characterised a large panel of vaginal Lactobacillus strains from young African women (including growth, adhesion to host cells, ability to produce antimicrobial products, and pathogen inhibition), compared to isolates from commercial probiotic products for vaginal health. We also sequenced the genomes of top-performing isolates. Several vaginal Lactobacillus strains exhibited better probiotic profiles than commercial strains, suggesting that they would be beneficial in the development of probiotic treatment of bacterial vaginosis. A wider range of well-characterized Lactobacillus-containing probiotics may improve bacterial vaginosis treatment outcomes, which would hopefully lower the burden of adverse pregnancy outcomes and sexually transmitted infections.
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