Parolin Carola, Frisco Giulia, Foschi Claudio, Giordani Barbara, Salvo Melissa, Vitali Beatrice, Marangoni Antonella, Calonghi Natalia
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Microbiology, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
Front Microbiol. 2018 Nov 6;9:2630. doi: 10.3389/fmicb.2018.02630. eCollection 2018.
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 . This study aimed to elucidate the molecular bases of the interaction among vaginal lactobacilli, the sexually transmitted pathogen and the epithelial cervical cells. We evaluated the activity of 15 strains, belonging to different species (i.e., , ), against . In particular, we evaluated the capability of lactobacilli cells to interfere with infection in HeLa cells, by exclusion assays. Lactobacilli significantly reduced infectivity, being 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., , , and ) failed to interfere with infectivity, activity proved to be specific. The potential mechanism of protection was investigated in 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 gene expression was silenced, infection was significantly reduced. It follows that α5 integrin subunit is crucial for the pathogen infection process, and the anti- 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 BC5 against , getting insights into the role of the cervico-vaginal microbiota for the woman's health.
乳酸杆菌在维持阴道微生态平衡、防止外源微生物定植方面发挥着关键作用。尽管许多研究已经探讨了乳酸杆菌对抗几种泌尿生殖病原体所显示的机制,但关于乳酸杆菌与……之间相互作用的数据却很少。本研究旨在阐明阴道乳酸杆菌、性传播病原体……与宫颈上皮细胞之间相互作用的分子基础。我们评估了15株属于不同物种(即……)的……菌株对……的……活性。特别是,我们通过排除试验评估了乳酸杆菌细胞干扰HeLa细胞中……感染的能力。乳酸杆菌显著降低了……的感染性,……是最具活性的物种。尽管观察到剂量依赖性效应,但即使在较低剂量下也保持了显著的拮抗活性。由于其他革兰氏阳性菌(即……)未能干扰……的感染性,……活性被证明是特异性的。在被选为模型菌株的……BC5中研究了潜在的保护机制。HeLa细胞系与BC5细胞共孵育通过改变脂质组成和α5整合素亚基暴露诱导了上皮质膜的重要变化。当α5整合素亚基被特异性阻断抗体掩盖或……基因表达沉默时,……感染显著降低。由此可见,α5整合素亚基对病原体感染过程至关重要,抗……活性可能与宫颈细胞中的膜特性改变直接相关。用作对照的三种革兰氏阳性菌未能改变α5β1整合素的表达。总之,我们确定了……BC5对……发挥保护作用的潜在分子机制,深入了解了宫颈阴道微生物群对女性健康的作用。