Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils

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

Research output: Contribution to journalArticle

416 Scopus citations

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 monse 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.

Original languageEnglish (US)
Pages (from-to)3907-3919
Number of pages13
JournalJournal of Immunology
Volume175
Issue number6
DOIs
StatePublished - Sep 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Insights into mechanisms used by Staphylococcus aureus to avoid destruction by human neutrophils'. Together they form a unique fingerprint.

Cite this