Cited by 563Antimicrobial Resistance in StaphylococcusNeutrophil, Myeloperoxidase and Oxidative MechanismsStreptococcal Infections and Treatments

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Insights into Mechanisms Used by Staphylococcus aureus to Avoid Destruction by Human Neutrophils

Voyich, Jovanka M, Braughton, Kevin R, Sturdevant, Daniel E, Whitney, Adeline R, Saïd-Salim, Battouli, Porcella, Stephen F, Long, R Daniel, Dorward, David W, Gardner, Donald J, Kreiswirth, Barry N, Musser, James M, DeLeo, Frank R·2005·The Journal of Immunology

DOI 10.4049/jimmunol.175.6.3907

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Abstract

Polymorphonuclear leukocytes (PMNs, or neutrophils) are critical for human innate immunity and kill most invading bacteria. However, pathogens such as Staphylococcus aureus avoid destruction by PMNs to survive, thereby causing human infections. The molecular mechanisms used by pathogens to circumvent killing by the immune system remain largely undefined. To that end, we studied S. aureus pathogenesis and bacteria-PMN interactions using strains originally isolated from individuals with community-acquired (CA) and hospital-acquired infections. Compared with strains from hospital infections (COL and MRSA252), strain MW2 and a methicillin-susceptible relative, MnCop, were significantly more virulent in a mouse model of S. aureus infection, and caused the greatest level of pathology in major vital organs. Although phagocytosis of each strain triggered production of reactive oxygen species and granule-phagosome fusion, those from CA infections were significantly more resistant to killing by human PMNs and caused greater host cell lysis. Microarray analysis of the strains during neutrophil phagocytosis identified genes comprising a global S. aureus response to human innate host defense. Genes involved in capsule synthesis, gene regulation, oxidative stress, and virulence, were up-regulated following ingestion of the pathogen. Notably, phagocytosis of strains from CA infections induced changes in gene expression not observed in the other strains, including up-regulation of genes encoding virulence factors and hypothetical proteins. Our studies reveal a gene transcription program in a prominent human pathogen that likely contributes to evasion of innate host defense.

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Authors: Voyich, J. M., Braughton, K. R., Sturdevant, D. E., Whitney, A. R., Saïd-Salim, B., Porcella, S. F., Long, R. D., Dorward, D. W., Gardner, D. J., Kreiswirth, B. N., Musser, J. M., & DeLeo, F. R.
Affiliations: National Institutes of Health (US)
Public Health Research Institute Tuberculosis Center, International Center for Public Health , Newark, NJ 07103
International Center for Public Health (US)
Baylor College of Medicine (US)
ORCID: Voyich, Jovanka M
Porcella, Stephen F
Dorward, David W
Kreiswirth, Barry N
Musser, James M
DeLeo, Frank R
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2005-09
Volume: 175
Issue: 6
Pages: 3907-3919
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.175.6.3907
OpenAlex: W1848320945
Cited by: 563
References: 58
Citations by year: 2026: 5 · 2025: 17 · 2024: 25 · 2023: 10 · 2022: 20 · 2021: 16 · 2020: 17 · 2019: 23 · 2018: 29 · 2017: 34 · 2016: 29 · 2015: 31 · 2014: 33 · 2013: 49 · 2012: 43
FWCI: 12.79
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Health Sciences › Medicine › Infectious Diseases › Streptococcal Infections and Treatments
Keywords: Staphylococcus aureus, polymorphonuclear leukocytes, innate immunity, phagocytosis, community-acquired infections, nosocomial infections, virulence, capsule synthesis, oxidative stress, gene expression response, virulence factors, methicillin-resistant Staphylococcus aureus, host-pathogen interaction
MeSH terms: Genes, Bacterial, Humans, Immunity, Innate, Neutrophils, Phagocytosis, Staphylococcal Infections, Staphylococcus aureus, Gene Expression Regulation, Bacterial, Gene Expression Profiling, Virulence Factors

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Insights into Mechanisms Used by Staphylococcus aureus to Avoid Destruction by Human Neutrophils

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