agr-Dependent Interactions of Staphylococcus aureus USA300 with Human Polymorphonuclear Neutrophils
- 10 September 2010
- journal article
- research article
- Published by S. Karger AG in Journal of Innate Immunity
- Vol. 2 (6), 546-559
- https://doi.org/10.1159/000319855
Abstract
The emergence of serious infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has fueled interest in the contributions of specific staphylococcal virulence factors to clinical disease. To assess the contributions of agr-dependent factors to the fate of organisms in polymorphonuclear neutrophils (PMN), we examined the consequences for organism and host cells of feeding PMN with wild-type CA-MRSA (LAC) or CA-MRSA (LAC agr KO) at different multiplicities of infection (MOIs). Phagocytosed organisms rapidly increased the transcription of RNAIII in a time- and MOI-dependent fashion; extracellular USA300 (LAC) did not increase RNAIII expression despite having the capacity to respond to autoinducing peptide-enriched culture medium. HOCl-mediated damage and intracellular survival were the same in the wild-type and USA300 (LAC agr KO). PMN lysis by ingested USA300 (LAC) was time- and MOI-dependent and, at MOIs >1, required α-hemolysin (hla) as USA300 (LAC agr KO) and USA300 (LAC hla KO) promoted PMN lysis only at high MOIs. Taken together, these data demonstrate activation of the agr operon in human PMN with the subsequent production of α-hemolysin and PMN lysis. The extent to which these events in the phagosomes of human PMN contribute to the increased morbidity and mortality of infections with USA300 (LAC) merits further study.Keywords
This publication has 42 references indexed in Scilit:
- Epidemic community-associated methicillin-resistant Staphylococcus aureus : Recent clonal expansion and diversificationProceedings of the National Academy of Sciences of the United States of America, 2008
- Neutrophil Microbicides Induce a Pathogen Survival Response in Community-Associated Methicillin-Resistant Staphylococcus aureusThe Journal of Immunology, 2008
- Poring over pores: α-hemolysin and Panton-Valentine leukocidin in Staphylococcus aureus pneumoniaNature Medicine, 2007
- Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSANature Medicine, 2007
- How human neutrophils kill and degrade microbes: an integrated viewImmunological Reviews, 2007
- Global analysis of community-associated methicillin-resistant Staphylococcus aureus exoproteins reveals molecules produced in vitro and during infectionCellular Microbiology, 2007
- Surface Proteins and Exotoxins Are Required for the Pathogenesis ofStaphylococcus aureusPneumoniaInfection and Immunity, 2007
- Isolation of Human Neutrophils From Venous BloodPublished by Springer Science and Business Media LLC ,2007
- Transmembrane β-barrel of staphylococcal α-toxin forms in sensitive but not in resistant cellsProceedings of the National Academy of Sciences of the United States of America, 1997
- Cell density control of staphylococcal virulence mediated by an octapeptide pheromone.Proceedings of the National Academy of Sciences of the United States of America, 1995