Mutation in Staphylococcus aureus that supports gain of function in susceptibility both to hypochlorous acid and to human neutrophils

Athmane Teghanemt; Katrin Schilcher; Jeffery S Kavanaugh; Alexander R Horswill; William M Nauseef

doi:10.1093/jleuko/qiaf057

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Mutation in Staphylococcus aureus that supports gain of function in susceptibility both to hypochlorous acid and to human neutrophils

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Mutation in Staphylococcus aureus that supports gain of function in susceptibility both to hypochlorous acid and to human neutrophils

Athmane Teghanemt, Katrin Schilcher, Jeffery S Kavanaugh, Alexander R Horswill and William M Nauseef

Journal of leukocyte biology, Vol.117(7), qiaf057

07/09/2025

DOI: 10.1093/jleuko/qiaf057

PMCID: PMC12239878

PMID: 40388361

Appears in UI Libraries Support Open Access

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Abstract

Optimal antimicrobial action of human neutrophils (polymorphonuclear leukocytes [PMNs]) relies on the synergy of oxidants and granule proteins, most notably that between the granule protein myeloperoxidase (MPO) and hydrogen peroxide (H2O2) to oxidize chloride anion to produce the potent microbicide, hypochlorous acid (HOCl). However, despite the potency of HOCl, some ingested Staphylococcus aureus cells survive within PMNs and contribute to disease. To identify factors that support the resistance of ingested staphylococci to PMN-oxidative killing, we screened the Nebraska Transposon Mutant Library in the USA300 methicillin-resistant S. aureus strain for mutants that were more sensitive or resistant to HOCl. We identified a mutant in mazF that survived challenge with reagent HOCl better than did the parental strain. In addition, the mutant resisted killing by human PMNs, suggesting that MazF contributes to the susceptibility of S. aureus to HOCl-mediated damage, the ability of S. aureus to recover from HOCl attack, or both. To confirm the genetic basis of the MazF phenotypes, we transformed the mutant with an expression plasmid carrying the wild-type mazF gene or the empty vector control to complement the phenotype. The deletion mutant with the empty vector survived better in reagent HOCl and in PMNs than did the parental strain or the complemented deletion mutant. Taken together, these data suggest that in the absence of mazF expression, USA300 methicillin-resistant S. aureus better resisted, repaired, or both resisted and repaired the sublethal damage produced by HOCl alone or by antimicrobial elements in human PMNs.

Mutation

Bacterial Proteins - genetics

Gain of Function Mutation

Humans

Hypochlorous Acid - pharmacology

Methicillin-Resistant Staphylococcus aureus - drug effects

Methicillin-Resistant Staphylococcus aureus - genetics

Neutrophils - immunology

Neutrophils - microbiology

Staphylococcal Infections - immunology

Staphylococcus aureus - drug effects

Staphylococcus aureus - genetics

UIOWA OA Agreement

Details

Title: Subtitle: Mutation in Staphylococcus aureus that supports gain of function in susceptibility both to hypochlorous acid and to human neutrophils
Creators: Athmane Teghanemt - University of Iowa, Internal Medicine
Katrin Schilcher - University of Colorado Anschutz Medical Campus
Jeffery S Kavanaugh - University of Colorado Anschutz Medical Campus
Alexander R Horswill - University of Colorado Anschutz Medical Campus
William M Nauseef - University of Iowa, Infectious Diseases
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.117(7), qiaf057
DOI: 10.1093/jleuko/qiaf057
PMID: 40388361
PMCID: PMC12239878
NLM abbreviation: J Leukoc Biol
ISSN: 1938-3673
eISSN: 1938-3673
Publisher: Oxford University Press
Grant note: R01 AI132335 / NIAID NIH HHS BX002711 / U.S. Department of Veterans Affairs Merit Award 20POST35220011 / American Heart Association AI146543 / NIH HHS AI116546 / NIH HHS R21 AI146543 / NIAID NIH HHS I01 BX002711 / BLRD VA R01 AI116546 / NIAID NIH HHS AI132335 / NIH HHS
Language: English
Electronic publication date: 05/28/2025
Date published: 07/09/2025
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984847841202771

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