Lactobacillus crispatus BC5 Interferes With Chlamydia trachomatis Infectivity Through Integrin Modulation in Cervical Cells
Lactobacillus crispatus BC5 Interferes With Chlamydia trachomatis Infectivity Through Integrin Modulation in Cervical Cells
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DOI：
10.3389/fmicb.2018.02630
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发表时间：
2018-11-06
影响因子：
5.2
通讯作者：
Calonghi, Natalia
中科院分区：
文献类型：
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作者：
Parolin, Carola;Frisco, Giulia;Calonghi, Natalia
乳酸杆菌在维持阴道生态位的生态平衡，防止外源性微生物的定植方面起着至关重要的作用。虽然许多研究已经讨论了乳酸杆菌在抵抗几种泌尿生殖道病原体中所显示的机制，但关于乳酸杆菌和沙眼衣原体之间的相互作用的数据很少。本研究旨在阐明性传播病原体阴道乳杆菌之间相互作用的分子基础。沙眼和宫颈上皮细胞。我们评估了属于不同物种的15种乳杆菌菌株的体外活性（即，L. crispatus，L.加塞里湖vagelis），对C.沙眼特别地，我们评估了乳酸杆菌细胞干扰C.沙眼衣原体感染的HeLa细胞，通过排除测定。乳酸杆菌显著降低了C.沙眼衣原体感染性，为L. crispatus是最活跃的物种。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。作为其他革兰氏阳性细菌（即，无乳链球菌、粪肠球菌和枯草芽孢杆菌）不能干扰C。沙眼衣原体的感染性，乳酸杆菌活性证明是特异性的。以卷曲乳杆菌（LactobacilluscrispatusBC5）为模型菌株，研究了其保护作用的可能机制。HeLa细胞系与BC5细胞的孵育通过改变脂质组成和α 5整联蛋白亚基暴露诱导上皮细胞质膜的重要修饰。当α 5整合素亚基被特异性阻断抗体掩蔽或ITGA 5基因表达沉默时，衣原体感染显著减少。因此，α 5整联蛋白亚基在病原体感染过程中至关重要，并且抗衣原体活性可以直接与宫颈细胞中的膜性质改变相关。用作对照的三种革兰氏阳性细菌不能改变α 5 β 1整联蛋白的表达。总之，我们确定了一个潜在的分子机制的基础上发挥的保护作用的L。crispatus BC5对C.沙眼，深入了解宫颈阴道微生物群对女性健康的作用。
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 alpha 5 integrin subunit exposure. When alpha 5 integrin subunits were masked by a specific blocking antibody or ITGA5 gene expression was silenced, Chlamydia infection was significantly reduced. It follows that alpha 5 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 Grampositive bacteria used as controls failed to modify the expression of alpha 5 beta 1 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.