Department of Infection Biology, Interfaculty Institute for Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany
Cluster of Excellence "Controlling Microbes to Fight Infections," University of Tübingen, Tübingen, Germany.
mSphere. 2020 Sep 30;5(5):e00804-20. doi: 10.1128/mSphere.00804-20.
is a major pathogen, which colonizes one in three otherwise healthy humans. This significant spread of is largely due to its ability to circumvent innate immune responses, including antimicrobial fatty acids (AFAs) on the skin and in nasal secretions. In response to AFAs, swiftly induces resistance mechanisms, which have yet to be completely elucidated. Here, we identify membrane vesicle (MV) release as a resistance strategy used by to sequester host-specific AFAs. MVs protect against a wide array of AFAs. Strikingly, beside MV production, modulates MV composition upon exposure to AFAs. MVs purified from bacteria grown in the presence of linoleic acid display a distinct protein content and are enriched in lipoproteins, which strongly activate Toll-like receptor 2 (TLR2). Cumulatively, our findings reveal the protective capacities of MVs against AFAs, which are counteracted by an increased TLR2-mediated innate immune response. The nares of one in three humans are colonized by In these environments, and arguably on all mucosal surfaces, bacteria encounter fatty acids with antimicrobial properties. Our study uncovers that releases membrane vesicles (MVs) that act as decoys to protect the bacterium against antimicrobial fatty acids (AFAs). The AFA-neutralizing effects of MVs were neither strain specific nor restricted to one particular AFA. Hence, MVs may represent "public goods" playing an overlooked role in shaping bacterial communities in AFA-rich environments such as the skin and nose. Intriguingly, in addition to MV biogenesis, modulates MV composition in response to exposure to AFAs, including an increased release of lipoproteins. These MVs strongly stimulate the innate immunity via Toll-like receptor 2 (TLR2). TLR2-mediated inflammation, which helps to fight infections, may exacerbate inflammatory disorders like atopic dermatitis. Our study highlights intricate immune responses preventing infections from colonizing bacteria.
是一种主要的病原体，它定植于三分之一的健康人类个体中。这种的广泛传播在很大程度上归因于其规避固有免疫反应的能力，包括皮肤和鼻腔分泌物中的抗菌脂肪酸（AFAs）。为了应对 AFAs，迅速诱导出抵抗机制，但这些机制尚未完全阐明。在这里，我们发现膜囊泡（MV）的释放是一种抵抗策略，可用于将宿主特异性 AFAs 隔离。MV 保护免受广泛的 AFAs 的侵害。引人注目的是，除了 MV 的产生之外，在暴露于 AFAs 时还会调节 MV 的组成。从在亚油酸存在下生长的细菌中纯化的 MV 显示出独特的蛋白质含量，并富含强烈激活 Toll 样受体 2（TLR2）的脂蛋白。总之，我们的研究结果揭示了 MV 对 AFAs 的保护能力，而 TLR2 介导的固有免疫反应会对抗这种保护能力。三分之一的人类鼻腔中都定植着。在这些环境中，并且可以说在所有粘膜表面上，细菌都会遇到具有抗菌特性的脂肪酸。我们的研究揭示了释放膜囊泡（MVs），这些囊泡充当诱饵，以保护细菌免受抗菌脂肪酸（AFAs）的侵害。MV 对 AFA 的中和作用既不是菌株特异性的，也不限于一种特定的 AFA。因此，MV 可能代表“公共物品”，在富含 AFA 的环境（如皮肤和鼻子）中塑造细菌群落方面发挥着被忽视的作用。有趣的是，除了 MV 的生物发生外，还会响应 AFAs 的暴露来调节 MV 的组成，包括脂蛋白的释放增加。这些 MV 通过 Toll 样受体 2（TLR2）强烈刺激先天免疫。有助于对抗感染的 TLR2 介导的炎症可能会加剧特应性皮炎等炎症性疾病。我们的研究强调了复杂的免疫反应，可防止感染定植细菌。
