Vaginal Lactobacillus mode of growth influences anti-Candida activity

Lactobacilli are the dominant members of the healthy human vaginal microbiota and represent the first defense line from pathogen infection, including vulvovaginal candidiasis caused by Candida species overgrowth. Microorganisms’ growth can occur in two modalities: the free form (planktonic) and the sessile form (biofilm). Biofilm is the predominant form in nature and its formation inside the human body has important implications in health and disease. Indeed, in a healthy microbiota, biofilm made-up by beneficial lactobacilli is desirable while biofilm from opportunistic pathogens is to be avoided since it supports tissues invasiveness. Here, culture supernatants derived from 16 vaginal Lactobacillus strains, grown in biofilm and planktonic forms, were tested toward a panel of Candida clinical isolates (Candida albicans, Candida glabrata, Candida lusitaniae, Candida tropicalis, Candida krusei, and Candida parapsilosis) and their metabolome assessed by 1H-NMR. The effect of Lactobacillus supernatants was also evaluated toward Candida biofilm formation. We were able to correlate Lactobacillus mode of growth with their metabolism and the anti-Candida activity. Strains belonging to Lactobacillus crispatus and Lactobacillus plantarum exhibited the best anti-Candida profile, and biofilm enhanced their activity; on the contrary, Lactobacillus gasseri strains were more effective when grown in a planktonic mode. Lactobacillus mode of growth affects their metabolism, mainly influencing nitrogen and amino acid pathways while the anti-Candida activity is instead strictly related to carbohydrate metabolism. Here, we found a strict interdependence between microbial mode of growth, metabolism, and functional properties. This study provides new evidence in the field of vaginal microbial physiology and host–microbiota interactions, beyond supporting the development of new antimycotic strategies based on biofilm-forming probiotics.