Mechanosensitive Channels: Utilising the Bacterial Cell’s Defence Mechanism against It

Abstract

Mechanosensitive channels are integral membrane proteins in bacterial cell membranes as well as archaea, and eukaryotes. The role of these bacterial mechanosensitive channels is essential for protecting cells from structural damage during hypoosmotic shock. Mechanosensitive channel of small conductance (MscS) and mechanosensitive channels of large conductance (MscL) are the predominant channels in E. coli. Activation of mechanosensitive channels typically occurs when the bacterial membrane senses tension or distortion. Overall, the ecological niche of bacteria shapes the selective pressures acting on mechanosensitive channels, leading to their adaptation to specific environmental conditions. Bacterial mechanosensitive channels contribute to the ability of bacterial pathogens to adapt to and survive within the host environment, as well as to modulate interactions with host cells and tissues during infection. They could also act as entrance gates for specific antibiotic classes into bacterial cells. Accordingly, it was discovered that nitrofuran nifuroxazide and tuberactinomycin viomycin depended on both Ec-MscS and Ec-MscL for enhanced efficacy. Several compounds have been identified that directly target mechanosensitive channels. For example, ramizol has been shown to reduce the gating threshold of MscL and MscS channels, while styrylbenzene inhibits MscL channels in S. aureus, Streptococcus pneumoniae, and Clostridium difficile. Bacterial mechanosensitive channels are versatile drug targets due to their role in promoting bacterial virulence and host colonization, serving as entry points for antibiotics, and being structurally distinct from mammalian counterparts. These special structures which are meant to protect the cell can also be harnessed as drug targets, thereby increasing the susceptibility of the bacterial cell to target antibiotics. This feature has been harnessed to reduce the burden of antibiotics resistance and its attendant effect on global healthcare complications. The aim of this review is to examine the various physiological, drug resistance and pathogenicity roles of these mechanosensitive channels as well as their usefulness as potential drug targets.