Bacterial and fungal thiol-containing enzymes and structural proteins

Bacterial and fungal thiol-containing enzymes and structural proteins represent a broad class of essential microbial targets characterized by the presence of reactive sulfhydryl (-SH) groups on cysteine residues (Ankri & Mirelman, 1999). These groups are vital for the catalytic function of numerous enzymes involved in central metabolism, such as dehydrogenases and thioredoxin reductase, as well as for maintaining the structural stability of various cellular proteins through disulfide bridge formation (Clarkson & Magos, 2006). Antimicrobial agents like silver ions, organomercurials, and certain plant-derived electrophiles like allicin exert their effects by binding to these thiols, causing widespread protein dysfunction and metabolic collapse (Slavin et al., 2017). This multi-target mechanism is effective against a wide range of pathogens, including antibiotic-resistant bacteria and various fungal species (Jung et al., 2008). However, because thiol groups are ubiquitous in both pathogens and human host cells, drugs targeting this group often face challenges regarding selectivity and systemic toxicity. Consequently, therapeutic use is frequently limited to topical applications, wound dressings, or disinfectants to minimize adverse effects on the host (StatPearls, 2023).

Other names

Sulfhydryl-containing microbial proteinsThiol-dependent microbial enzymesMicrobial thiol proteome

Antimicrobial agents targeting these proteins typically act via covalent modification or coordination with the sulfhydryl (-SH) groups of cysteine residues (Slavin et al., 2017). This interaction leads to the inhibition of enzymatic activity, disruption of disulfide bond formation, protein denaturation, and the induction of oxidative stress within the microbial cell (Jung et al., 2008).