Staphylococcus aureus senses human neutrophils via PerR to coordinate the expression of the toxin LukAB
Open accessAbstract
Staphylococcus aureus is a gram-positive pathogen that poses a major health concern, in part due to its large array of virulence factors that allow infection and evasion of the immune system. One of these virulence factors is the bicomponent pore-forming leukocidin LukAB. The regulation of lukAB expression is not completely understood, especially in the presence of immune cells such as human polymorphonuclear neutrophils (hPMNs). Here, we screened for transcriptional regulators of lukAB during the infection of primary hPMNs. We uncovered that PerR, a peroxide sensor, is vital for hPMN-mediated induction of lukAB and that PerR upregulates cytotoxicity during the infection of hPMNs. Exposure of S. aureus to hydrogen peroxide (H 2 O 2 ) alone also results in increased lukAB promoter activity, a phenotype dependent on PerR. Collectively, our data suggest that S. aureus uses PerR to sense the H 2 O 2 produced by hPMNs to stimulate the expression of lukAB , allowing the bacteria to withstand these critical innate immune cells. IMPORTANCE: Staphylococcus aureus utilizes a diverse set of virulence factors, such as leukocidins, to subvert human neutrophils, but how these toxins are regulated is incompletely defined. Here, we identified the peroxide-sensitive repressor, PerR, as a required protein involved in the induction of lukAB in the presence of primary human neutrophils, a phenotype directly linked to the ability of PerR to sense H 2 O 2 . Thus, we show that S. aureus coordinates sensing and resistance to oxidative stress with toxin production to promote pathogen survival.
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PerR positively regulates the lukAB genes encoding the LukAB leukocidin.
“Recent work has revealed that PerR positively regulates the lukAB genes encoding the LukAB leukocidin (44) and thus links the ROS sensing to S. aureus toxin production.”
From The oxidative stress regulator, PerR, is required for staphyloferrin B-mediated iron acquisition in <i>Staphylococcus aureus</i> (2026) · cites this paper as [44]
PerR links ROS sensing to S. aureus toxin production.
“Recent work has revealed that PerR positively regulates the lukAB genes encoding the LukAB leukocidin (44) and thus links the ROS sensing to S. aureus toxin production.”
From The oxidative stress regulator, PerR, is required for staphyloferrin B-mediated iron acquisition in <i>Staphylococcus aureus</i> (2026) · cites this paper as [44]
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Sorted by citations
Sheikh, A. A., Flannagan, R. S., Nicholson, N. J., Jarycki, N., Fabelurin, R. O., Lewis, I. A., & Heinrichs, D. E. (2026) · Journal of Bacteriology · doi:10.1128/jb.00149-26
- Authors
- Savin, A., Anderson, E. E., Dyzenhaus, S., Podkowik, M., Shopsin, B., Pironti, A., & Torres, V. J.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Torres, Victor J.
- ORCID
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2024-02-13
- Volume
- 92
- Issue
- 2
- Pages
- e0052623-e0052623
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC10863418
- OpenAlex
- W4390974271
- Cited by
- 9
- References
- 75
- Citations by year
- 2026: 4 · 2025: 5
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Infection and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- American Lebanese Syrian Associated Charities
- Imperial College London
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI099394, R01AI137336, AI137336, R01AI099394)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Staphylococcus aureus, PerR, leukocidin, human neutrophils, hydrogen peroxide detection, oxidative stress, virulence regulation, innate immune evasion, transcriptional regulation
- MeSH terms
- Bacterial Proteins, Humans, Hydrogen Peroxide, Leukocidins, Neutrophils, Staphylococcal Infections, Staphylococcus aureus, Virulence Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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