title: Staphylococcus aureus elaborates leukocidin AB to mediate escape from within human neutrophils.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) strains of the pulsed-field type USA300 are primarily responsible for the current community-associated epidemic of MRSA infections in the United States. The success of USA300 is partly attributed to the ability of the pathogen to avoid destruction by human neutrophils (polymorphonuclear leukocytes [PMNs]), which are crucial to the host immune response to S. aureus infection. In this work, we investigated the contribution of bicomponent pore-forming toxins to the ability of USA300 to withstand attack from primary human PMNs. We demonstrate that in vitro growth conditions influence the expression, production, and availability of leukotoxins by USA300, which in turn impact the cytotoxic potential of this clone toward PMNs. Interestingly, we also found that upon exposure to PMNs, USA300 preferentially activates the promoter of the lukAB operon, which encodes the recently identified leukocidin AB (LukAB). LukAB elaborated by extracellular S. aureus forms pores in the plasma membrane of PMNs, leading to PMN lysis, highlighting a contribution of LukAB to USA300 virulence. We now show that LukAB also facilitates the escape of bacteria engulfed within PMNs, in turn enabling the replication and outgrowth of S. aureus. Together, these results suggest that upon encountering PMNs S. aureus induces the production of LukAB, which serves as an extra- and intracellular weapon to protect the bacterium from destruction by human PMNs.
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, New York, USA.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: DuMont
authors.forename: Pauline
authors.initials: P
authors.lastname: Yoong
authors.forename: Bas G J
authors.initials: BG
authors.lastname: Surewaard
authors.forename: Meredith A
authors.initials: MA
authors.lastname: Benson
authors.forename: Reindert
authors.initials: R
authors.lastname: Nijland
authors.forename: Jos A G
authors.initials: JA
authors.lastname: van Strijp
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007956:Leukocidins / Q000378:metabolism*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000502:physiology; D013203:Staphylococcal Infections / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology; D014774:Virulence / Q000502:physiology; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D007956:Leukocidins; D037521:Virulence Factors