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

Abstract

A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus 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 C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(−) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, 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 C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin.

Association of Chlamydia trachomatis burden with the vaginal microbiota, bacterial vaginosis, and metronidazole treatment

“…However, IFU : GCN ratios are only one of many parameters that have been used to contrast productive and persistent growth states, and other confirmatory approaches, such as morphological and transcriptional characterization of Ct forms, are required to more confidently differentiate Ct growth states ( Gérard et al., 2002 ; Belland et al., 2003 ; Gérard et al., 2004 ; Lewis et al., 2014 ). When individual bacterial species within these communities were examined, L. crispatus abundance was found to inversely correlate with both total and infectious chlamydial burden, consistent with published studies describing the partial protective effect of L. crispatus on Ct infection, potentially via the production of lactic acid and other metabolites or by modulation of inflammation in the genital tract ( O'Hanlon et al., 2013 ; Gong et al., 2014 ; Nardini et al., 2016 ; Anton et al., 2018 ; Edwards et al., 2019 ; Rastogi and Singh, 2022 ; Dong et al., 2023 ; Zalambani et al., 2023 ). Additionally, both total and infectious chlamydial burden positively correlated with the abundance of P. bivia , and IFU : GCN ratios with P. amnii .…”

Lactobacilli and lactic acid in maintaining and restoring women’s health

“…Зокрема, на відміну від своєї бактерицидної активності, D-молочна кислота пригнічує хламідійну інфекцію через рН-залежну дію на вагінальні епітеліальні клітини та мікрооточення [54]. Цей висновок випливає зі значно більшого захисту від хламідій, який забезпечують L. crispatus, L. gasseri та L. jensenii [54], що виробляють більше D-молочної кислоти, ніж L. iners, який виробляє переважно L-молочну кислоту [17].…”

Cervical HPV Infections, Sexually Transmitted Bacterial Pathogens and Cytology Findings—A Molecular Epidemiology Study

“…The possible mechanism of the association between UU infection and abnormal cervical cytopathology might be related to the combination of several complex infection-associated inflammatory responses, involving production of reactive oxidative metabolites, increased expression of cytokines, chemokines and growth and angiogenic factors, decreased cell-mediated immunity, and the generation of free radicals [40,46]. The large meta-analysis of Liang et al concluded that, together with bacterial vaginosis (BV), CT, and reduction in Lactobacilli, UU are also associated with increased risk of HPV infection and CIN development [40,47,48].…”