Cysteine import contributes to hypochlorous acid resistance in Staphylococcus aureus.

Authors

Abigail G Hall, Aliyah J Collins, Anna Sommers, Ryan Singh, Sasmita Panda, Sujata S Chaudhari, Andrew J Monteith, Vinai C Thomas

Published in

mSphere. Pages e0021426. Aug 24, 2026. Epub Aug 24, 2026.

Abstract

Hypochlorous acid (HOCl) is a potent antimicrobial oxidant produced by innate immune cells to eliminate invading bacterial pathogens, including Staphylococcus aureus. HOCl readily oxidizes thiols, amines, and macromolecules in S. aureus. Yet, some bacterial cells within an HOCl-challenged population withstand this oxidative stress and proceed to establish infection. The mechanisms that enable S. aureus to resist the effects of HOCl remain incompletely understood. Here, we show that cysteine uptake is a major determinant of HOCl resistance in S. aureus. Inactivation of the cysteine transporters tcyABC and tcyP resulted in a dose-dependent increase in sensitivity to HOCl. Cysteine uptake through these transporters helped maintain bacillithiol homeostasis and limit oxidative damage to protein thiols during HOCl stress. Importantly, cysteine uptake was required for the survival of S. aureus during interaction with activated human neutrophils that generate HOCl to kill phagocytosed bacteria. These findings reveal that cysteine uptake expands the thiol buffering capacity of S. aureus and functions as a major mechanism for scavenging HOCl, which may contribute to its persistence in the infected host.IMPORTANCEStaphylococcus aureus is a major human pathogen that causes recurrent and antibiotic-recalcitrant infections. Understanding the mechanisms that allow S. aureus to evade key innate immune defenses is therefore of considerable interest for developing effective intervention strategies. Our findings show that cysteine uptake is a critical component of S. aureus defense against hypochlorous acid (HOCl) produced by innate immune cells. Cysteine functions as a reactive sink for HOCl and thereby prevents depletion of both low-molecular-weight thiols and protein thiols in S. aureus.

PMID:
42635432
Bibliographic data and abstract were imported from PubMed on 24 Aug 2026.

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