Sidarta Margareth, Baruah Luna, Wenzel Michaela
Division of Chemical Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
Pharmaceuticals (Basel). 2022 Jun 21;15(7):770. doi: 10.3390/ph15070770.
Bacteria accumulate osmolytes to prevent cell dehydration during hyperosmotic stress. A sudden change to a hypotonic environment leads to a rapid water influx, causing swelling of the protoplast. To prevent cell lysis through osmotic bursting, mechanosensitive channels detect changes in turgor pressure and act as emergency-release valves for the ions and osmolytes, restoring the osmotic balance. This adaptation mechanism is well-characterized with respect to the osmotic challenges bacteria face in environments such as soil or an aquatic habitat. However, mechanosensitive channels also play a role during infection, e.g., during host colonization or release into environmental reservoirs. Moreover, recent studies have proposed roles for mechanosensitive channels as determinants of antibiotic susceptibility. Interestingly, some studies suggest that they serve as entry gates for antimicrobials into cells, enhancing antibiotic efficiency, while others propose that they play a role in antibiotic-stress adaptation, reducing susceptibility to certain antimicrobials. These findings suggest different facets regarding the relevance of mechanosensitive channels during infection and antibiotic exposure as well as illustrate that they may be interesting targets for antibacterial chemotherapy. Here, we summarize the recent findings on the relevance of mechanosensitive channels for bacterial infections, including transitioning between host and environment, virulence, and susceptibility to antimicrobials, and discuss their potential as antibacterial drug targets.
细菌积累渗透溶质以防止在高渗应激期间细胞脱水。突然转变为低渗环境会导致水分迅速涌入，使原生质体肿胀。为防止细胞因渗透破裂而裂解，机械敏感通道会检测膨压变化，并充当离子和渗透溶质的应急释放阀，从而恢复渗透平衡。就细菌在土壤或水生栖息地等环境中面临的渗透挑战而言，这种适应机制已得到充分研究。然而，机械敏感通道在感染过程中也发挥作用，例如在宿主定殖或释放到环境储库期间。此外，最近的研究提出机械敏感通道作为抗生素敏感性决定因素的作用。有趣的是，一些研究表明它们是抗菌药物进入细胞的入口，可提高抗生素效率，而另一些研究则提出它们在抗生素应激适应中发挥作用，降低对某些抗菌药物的敏感性。这些发现揭示了机械敏感通道在感染和抗生素暴露过程中的不同相关方面，也表明它们可能是抗菌化疗的有趣靶点。在此，我们总结了关于机械敏感通道与细菌感染相关性的最新发现，包括在宿主与环境之间转换、毒力以及对抗菌药物的敏感性，并讨论它们作为抗菌药物靶点的潜力。
