Multiple, non-specific microbial and host thiol-containing molecules and pathways

Multiple, non-specific microbial and host thiol-containing molecules and pathways refer to a broad class of biological entities characterized by the presence of reactive sulfhydryl (-SH) groups. These molecules, which include low-molecular-weight thiols like glutathione and mycothiol as well as cysteine residues in proteins, are essential for maintaining cellular redox homeostasis and enzymatic activity (Source 1.2.2, 1.2.5). Drugs that target these groups, such as silver compounds, disulfiram, and heavy metals, typically act by covalently binding to or oxidizing the thiols, which leads to protein denaturation and the collapse of microbial metabolism (Source 1.2.1, 1.2.3). While this non-specific mechanism provides potent broad-spectrum antimicrobial activity, it also poses a significant risk of host toxicity because human cells rely on similar thiol-dependent pathways for survival (Source 1.2.5). Consequently, these targets are most commonly exploited in topical antiseptics or in specific therapeutic contexts where the drug's distribution can be carefully managed. Understanding the complex interactions between drugs and the thiol-rich environment of both pathogens and hosts is critical for optimizing efficacy and minimizing adverse systemic effects (Source 1.2.4).

Other names

Sulfhydryl groupsThiol groupsProtein thiolsCysteine residuesLow-molecular-weight thiolsLMW thiolsRedox-active thiols

Covalent modification, oxidation, or coordination binding to sulfhydryl (-SH) groups, leading to the inactivation of essential enzymes, depletion of cellular antioxidant capacity (e.g., glutathione), and disruption of metabolic and signaling pathways.