Role of D(-)-Lactic Acid in Prevention of Infection in an In Vitro Model of HeLa Cells.

A vaginal microbiota dominated by certain species may have a protective effect against infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. strains producing the D(-)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(-)-lactic acid isomer in the prevention of infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of that releases both D(-) and L(+) isomers and a strain of that produces only the L(+) isomer. Initially, we demonstrated that was significantly more effective than in reducing infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of or , resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(-)- or L(+)-lactic acid isomers. Our findings suggest that D(-) lactic acid significantly affects two non-exclusive mechanisms involved in infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin.