Zalambani Chiara, Rizzardi Nicola, Marziali Giacomo, Foschi Claudio, Morselli Sara, Djusse Marielle Ezekielle, Naldi Marina, Fato Romana, Calonghi Natalia, Marangoni Antonella
Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy.
Microbiology, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy.
Pathogens. 2023 Jun 28;12(7):883. doi: 10.3390/pathogens12070883.
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.
由某些特定菌种主导的阴道微生物群可能对感染具有保护作用。所产生的关键抗菌化合物之一是乳酸，据信其在宿主防御中发挥核心作用。已知产生D(-)-乳酸异构体的菌株具有更强的保护作用。然而，这种抗菌作用的分子机制尚未完全了解。本研究的目的是在体外HeLa细胞模型中研究D(-)-乳酸异构体在预防感染中的作用。我们选择了两株属于不同菌种的乳酸杆菌：一株阴道分离株，它能释放D(-)和L(+)两种异构体，以及一株只产生L(+)异构体的菌株。最初，我们证明在降低感染性方面，前者比后者显著更有效。当用前者或后者的上清液对HeLa细胞进行24小时预处理时，观察到组蛋白乙酰化和乳酰化的模式不同，导致CCND1、CDKN1A、ITAG5和HER-1等基因的转录不同。同样，在用10 mM D(-)-或L(+)-乳酸异构体处理的HeLa细胞中也发现了不同的转录模式。我们的研究结果表明，D(-)乳酸显著影响感染过程中涉及的两种非排他性机制：细胞周期调控以及表皮生长因子受体（EGFR）和α5β1整合素的表达。
