Microbial cellular thiol-containing proteins and small molecules

Microbial cellular thiol-containing proteins and small molecules represent a broad yet critical class of therapeutic targets essential for the survival and virulence of various pathogens. These targets include low-molecular-weight thiols like glutathione, mycothiol, and bacillithiol, which are indispensable for maintaining cellular redox homeostasis and protecting against oxidative damage (Fahey, 2013, Free Radical Biology and Medicine). Furthermore, many essential microbial enzymes contain highly reactive cysteine residues within their active sites that are necessary for catalytic function (Lemire et al., 2013, Nature Reviews Microbiology). Antimicrobial agents, including heavy metal ions like silver and mercury, as well as reactive oxygen species, exert their effects by covalently binding to or oxidizing these sulfhydryl groups (Lansdown, 2002, Journal of Wound Care). This interaction leads to the widespread inactivation of metabolic enzymes, disruption of protein folding, and the collapse of the cell's antioxidant defenses. Because these thiol-containing molecules are central to microbial physiology, targeting them provides a potent mechanism for broad-spectrum antimicrobial activity. However, the lack of high specificity for microbial versus host thiols remains a significant challenge in the development of systemic therapies.

Other names

Microbial thiolsBacterial sulfhydryl groupsMicrobial thiol-redox systemBacterial thiol-containing proteins

Covalent modification or oxidation of sulfhydryl (-SH) groups, leading to enzyme inactivation, protein denaturation, and depletion of cellular antioxidant capacity.