Thiol:disulfide interchange protein DsbA (DsbA)

Thiol:disulfide interchange protein DsbA is a critical periplasmic enzyme found in Gram-negative bacteria, where it serves as the primary catalyst for the formation of disulfide bonds in proteins [2, 11]. As a member of the thioredoxin-like superfamily, DsbA possesses a highly oxidizing redox potential, allowing it to efficiently transfer disulfide bonds to nascent polypeptides as they enter the periplasm [7, 12]. This oxidative folding is essential for the structural integrity and functional maturation of numerous virulence factors, including toxins, adhesins, and secretion system components [3, 10]. Consequently, DsbA is a major determinant of bacterial pathogenesis across a wide range of species, such as Escherichia coli, Pseudomonas aeruginosa, and Vibrio cholerae [9, 15]. Because DsbA is required for virulence but typically not for bacterial viability, it is considered an attractive target for the development of anti-virulence drugs [3, 4]. Such agents aim to disarm the pathogen without exerting the intense selective pressure that drives the emergence of antibiotic resistance [6, 13]. Current drug discovery efforts focus on small molecules, including covalent inhibitors and peptidomimetics, that block the DsbA active site or its substrate-binding groove [4, 9].

Other names

DsbAdsfppfAPeriplasmic protein disulfide isomeraseDithiol oxidase

Inhibition of DsbA-mediated oxidative folding of bacterial virulence factors, thereby attenuating pathogenesis without affecting bacterial viability.