Lactobacillus crispatus BC5 Interferes With Chlamydia trachomatis Infectivity Through Integrin Modulation in Cervical Cells

Abstract

Lactobacilli play a crucial role in maintaining the ecological equilibrium of the vaginal niche, preventing the colonization of exogenous microorganisms. Although many studies have discussed the mechanisms displayed by lactobacilli in counteracting several urogenital pathogens, a few data are available on the interaction between lactobacilli and Chlamydia trachomatis. This study aimed to elucidate the molecular bases of the interaction among vaginal lactobacilli, the sexually transmitted pathogen C. trachomatis and the epithelial cervical cells. We evaluated the in vitro activity of 15 Lactobacillus strains, belonging to different species (i.e., L. crispatus, L. gasseri, L. vaginalis), against C. trachomatis. In particular, we evaluated the capability of lactobacilli cells to interfere with C. trachomatis infection in HeLa cells, by exclusion assays. Lactobacilli significantly reduced C. trachomatis infectivity, being L. crispatus the most active species. Although a dose-dependent effect was noticed, a significant antagonistic activity was maintained even at lower doses. As other Gram-positive bacteria (i.e., Streptococcus agalactiae, Enterococcus faecalis, and Bacillus subtilis) failed to interfere with C. trachomatis infectivity, Lactobacillus activity proved to be specific. The potential mechanism of protection was investigated in Lactobacillus crispatus BC5, chosen as the model strain. The incubation of HeLa cell line with BC5 cells induced important modifications in the epithelial plasma membrane, by altering lipid composition and α5 integrin subunit exposure. When α5 integrin subunits were masked by a specific blocking antibody or ITGA5 gene expression was silenced, Chlamydia infection was significantly reduced. It follows that α5 integrin subunit is crucial for the pathogen infection process, and the anti-Chlamydia activity can be directly linked to membrane properties modifications in cervical cells. The three Gram-positive bacteria used as controls failed to modify the expression of α5β1 integrin. In conclusion, we identified a potential molecular mechanism at the basis of the protection exerted by L. crispatus BC5 against C. trachomatis, getting insights into the role of the cervico-vaginal microbiota for the woman’s health.

Chlamydia trachomatis and Chlamydia pneumoniae Interaction with the Host: Latest Advances and Future Prospective

“…Since then, several studies reported the ability of different vaginal Lactobacillus strains such as Lactobacillus brevis or Lactobacillus crispatus to strongly inhibit early phases of C. trachomatis infection as well as its intracellular replication. In particular, several potential mechanisms interfering with C. trachomatis adhesion to host cell have been described, including the increased production of lactate and consumption of glucose, the co-aggregation with EBs, the changes in lipid composition of the cell membrane as well as the modulation of the α5 integrin subunit [70,71,72]. As a further defense mechanism, L. brevis has been demonstrated to inhibit the development of C. trachomatis persistent forms induced by HSV-2 coinfection [70].…”

Biosurfactant from vaginal Lactobacillus crispatus BC1 as a promising agent to interfere with Candida adhesion

“…Lactobacilli are the predominant microorganisms in the vaginal microbiota of healthy women that contribute to preventing urogenital and sexually transmitted infections [3][4][5]. The protective role in the vagina is exerted through different mechanisms including: adhesion and permanence on the epithelium (promoted by biofilm formation), competitive exclusion against pathogens, production of antimicrobial compounds and/or modulation of the host's immune response [3,[6][7][8][9]. In this scenario, probiotics or pharmaceuticals containing lactobacilli or their derivatives represent a novel strategy to reconstitute the vaginal microbiota and prevent/treat urogenital infections [10,11].…”

Genome editing using the endogenous type I CRISPR-Cas system in Lactobacillus crispatus

“…The human vaginal microbiome is dominated by lactobacilli with Lactobacillus crispatus as one of the predominant species (31), which also plays a key role in poultry intestinal health (29) and has been implicated in the maintenance of a healthy status, whereas its absence is correlated with a higher risk of infectious disease (32,33). Moreover, L. crispatus has become an emerging probiotic for women's and poultry health due to its ability to fend off invasive pathogenic bacteria through competitive exclusion, production of antimicrobial compounds and exopolysaccharides (34)(35)(36), and elicitation of a beneficial host immune response (37). However, the genetic basis of the L. crispatus probiotic features remains unknown due to the lack of molecular tools available for this genetically refractory species.…”