Transcriptomic and Proteomic Analysis of Gardnerella vaginalis Responding to Acidic pH and Hydrogen Peroxide Stress

Abstract

Gardnerella vaginalis is the main pathogen that causes bacterial vaginosis. In the healthy vaginal microecological environment of a woman, the lactobacilli produce lactate and hydrogen peroxide to inhibit the growth of pathogens such as G. vaginalis. The lack of lactobacilli results in a high pH and low hydrogen peroxide in the vagina which facilitate G. vaginalis growth, leading to the imbalance of the vaginal microecology. In this study, lactate and hydrogen peroxide were added to a G. vaginalis culture medium to simulate the co-culture of the lactobacilli and G. vaginalis, and then the genes related to the stress response of G. vaginalis were identified using transcriptomics and proteomics. It was indicated that, among all the upregulated genes, most of them encoded transporters associated with the efflux of harmful substances, and the majority of the downregulated genes were related to the biofilm formation and epithelial cell adhesion. This study may help find new drug targets for G. vaginalis for the development of novel therapies for bacterial vaginosis.

Keywords: Gardnerella vaginalis; biofilm formation; lactate and hydrogen peroxide; lactobacilli; transcriptomics.

Figure 1

General comparison of the control, Lac group and LacHyd group. (A) Growth curves of the three groups. (B) Venn analysis of the shared genes that were upregulated compared to the control in the two groups. (C) Venn analysis of the shared genes that were downregulated compared to the control in the two groups. The pH values of the three groups were 7.0., 5.5 and 5.5, respectively; the H₂O₂ concentration of the LacHyd group was 0.5 mM.

Figure 2

Quantification of the transcription of the virulence genes that were expressed differentially in G. vaginalis cultured under lactate and hydrogen peroxide. Bars represent the mean, and the error bars the standard error of the mean (mean ± SEM).

Figure 3

The effect model of the lactobacilli on the biofilm formation of G. vaginalis. (A) Healthy vaginal microecosystem; (B) BV vaginal microecosystem.