Diverse Expression of Antimicrobial Activities Against Bacterial Vaginosis and Urinary Tract Infection Pathogens by Cervicovaginal Microbiota Strains of Lactobacillus gasseri and Lactobacillus crispatus.

Fabrice Atassi,Vanessa Lievin-Le Moal,Diane L. Pho Viet Ahn

doi:10.3389/fmicb.2019.02900

Abstract

We aimed to analyze the strain-by-strain expression of a large panel of antimicrobial activities counteracting the virulence mechanisms of bacterial vaginosis-associated Prevotella bivia CI-1 and Gardnerella vaginalis 594, pyelonephritis-associated Escherichia coli CFT073, and recurrent cystitis- and preterm labor-associated IH11128 E. coli by Lactobacillus gasseri and Lactobacillus crispatus clinical strains, and L. gasseri ATCC 9857 and KS 120.1, and L. crispatus CTV-05 strains isolated from the cervicovaginal microbiota of healthy women. All L. gasseri and L. crispatus strains exerted antimicrobial activity by secreted lactic acid, which killed the microbial pathogens by direct contact. Potent bactericidal activity was exerted by a very limited number of resident L. gasseri and L. crispatus strains showing the specific ability to a strain to produce and release antibiotic-like compounds. These compounds eradicated the microbial pathogens pre-associated with the surface of cervix epithelial cells, providing efficient protection of the cells against the deleterious effects triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Furthermore, these compounds crossed the cell membrane to kill the pre-internalized microbial pathogens. In addition, all L. gasseri and L. crispatus cells exhibited another non-strain specific activity which inhibited the association of microbial pathogens with cervix epithelial cells with varying efficiency, partially protecting the cells against lysis and detachment triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Our results provide evidence of strain-level specificity for certain antimicrobial properties among cervicovaginal L. gasseri and L. crispatus strains, indicating that the presence of a particular species in the vaginal microbiota is not sufficient to determine its benefit to the host. A full repertory of antimicrobial properties should be evaluated in choosing vaginal microbiota-associated Lactobacillus isolates for the development of live biotherapeutic strategies.

Highlights

Vaginal dysbiosis (De Seta et al, 2019), bacterial vaginosis (BV) (Onderdonk et al, 2016) and urinary-tract infections (UTIs) (Foxman, 2014) are major health problems that are difficult to treat and highly recurrent
L. gasseri KS 120.1 cell-free culture supernatants (CFCSs) exerted killing activity against P. bivia CI-1 and G. vaginalis 594 (6.43 ± 0.61 log10 and 6.35 ± 0.58 log10 CFU/ml decrease in viability, respectively), and uropathogenic Escherichia coli (UPEC) CFT073 and IH11128 (5.33 ± 0.56 and 5.04 ± 0.48 log10 CFU/ml decrease in viability, respectively), which largely persisted in the presence of Dulbecco’s modified Eagle’s minimum essential medium (DMEM) (P. bivia CI1: 4.20 ± 0.6, G. vaginalis 594: 4.30 ± 0.41, UPEC CFT073: 3.21 ± 0.67, and UPEC IH11128: 3.00 ± 0.47 log10 CFU/ml decrease in viability) (Figure 2A)
L. crispatus CTV-05 CFCS exerted killing activity, but to a lesser extent (P. bivia CI-1: 4.61 ± 0.53, G. vaginalis 594: 5.05 ± 0.42, UPEC CFT073: 3.51 ± 0.49, and UPEC IH11128: 4.23 ± 0.67 log10 CFU/ml decrease in viability), which was diminished by approximately one half in the presence of DMEM (P. bivia CI-1: 2.80 ± 0.68, G. vaginalis 594: 2.60 ± 0.41, UPEC CFT073: 1.72 ± 0.67, and UPEC IH11128: 2.31 ± 0.47 log10 CFU/ml decrease in viability)

Summary

Introduction

Vaginal dysbiosis (De Seta et al, 2019), bacterial vaginosis (BV) (Onderdonk et al, 2016) and urinary-tract infections (UTIs) (Foxman, 2014) are major health problems that are difficult to treat and highly recurrent. The human urogenital tract is colonized by a large diversity of microorganisms, representing a complex microbial ecosystem in which host and microbes exist in homeostasis (Whiteside et al, 2015; Smith and Ravel, 2017). The resilience of this ecosystem greatly depends on environmental exposure and behavioral factors, as well as a range of host factors, which vary between individuals, during life and geographically. The association between the risk of UTIs and the composition of the vaginal microbiota is still unclear (Whiteside et al, 2015)

Objectives

Methods

Results

Conclusion