title: agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils.
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.
authors.affiliation: Department of Medicine, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, Iowa 52241, USA.
authors.forename: Yun Yun
authors.initials: YY
authors.lastname: Pang
authors.forename: Jamie
authors.initials: J
authors.lastname: Schwartz
authors.forename: Matthew
authors.initials: M
authors.lastname: Thoendel
authors.forename: Laynez W
authors.initials: LW
authors.lastname: Ackermann
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Horswill
authors.forename: William M
authors.initials: WM
authors.lastname: Nauseef
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D017714:Community-Acquired Infections / Q000276:immunology* / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000472:pathogenicity / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics; D012329:RNA, Bacterial / Q000096:biosynthesis / Q000235:genetics; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D015534:Trans-Activators; D037521:Virulence Factors; C021091:staphylococcal alpha-toxin