Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.
Antimicrob Agents Chemother. 2011 Apr;55(4):1622-8. doi: 10.1128/AAC.00770-10. Epub 2011 Jan 18.
Lactobacilli are known to prevent colonization by many pathogens; nevertheless, the mechanisms of their protective effect are largely unknown. In this work, we investigated the role of lactobacilli during infection of epithelial cells with group A streptococci (GAS). GAS cause a variety of illnesses ranging from noninvasive disease to more severe invasive infections, such as necrotizing fasciitis and toxic shock-like syndrome. Invasion of deeper tissues is facilitated by GAS-induced apoptosis and cell death. We found that lactobacilli inhibit GAS-induced host cell cytotoxicity and shedding of the complement regulator CD46. Further, survival assays demonstrated that lactic acid secreted by lactobacilli is highly bactericidal toward GAS. In addition, lactic acid treatment of GAS, but not heat killing, prior to infection abolishes the cytotoxic effects against human cells. Since lipoteichoic acid (LTA) of GAS is heat resistant and cytotoxic, we explored the effects of lactic acid on LTA. By applying such an approach, we demonstrate that lactic acid reduces epithelial cell damage caused by GAS by degrading both secreted and cell-bound LTA. Taken together, our experiments reveal a mechanism by which lactobacilli prevent pathogen-induced host cell damage.
乳杆菌已知可以防止许多病原体的定植;然而,它们的保护作用机制在很大程度上尚不清楚。在这项工作中,我们研究了乳杆菌在与 A 组链球菌(GAS)感染上皮细胞过程中的作用。GAS 可引起多种疾病,从非侵入性疾病到更严重的侵袭性感染,如坏死性筋膜炎和中毒性休克样综合征。GAS 诱导的细胞凋亡和细胞死亡促进了对深部组织的侵袭。我们发现乳杆菌抑制 GAS 诱导的宿主细胞细胞毒性和补体调节因子 CD46 的脱落。此外,存活测定表明,乳杆菌分泌的乳酸对 GAS 具有高度杀菌作用。此外,在感染前用乳酸处理 GAS(而非热灭活)可消除对人细胞的细胞毒性作用。由于 GAS 的脂磷壁酸(LTA)耐热且具有细胞毒性,因此我们探讨了乳酸对 LTA 的作用。通过应用这种方法,我们证明乳酸通过降解分泌的和细胞结合的 LTA 来减少 GAS 引起的上皮细胞损伤。总之,我们的实验揭示了乳杆菌预防病原体引起的宿主细胞损伤的一种机制。