title: Identification of an intracellular M17 family leucine aminopeptidase that is required for virulence in Staphylococcus aureus.
abstract: Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing a variety of ailments throughout the human body. It is a major public health concern due to the continued emergence of highly pathogenic methicillin resistant strains (MRSA) both within hospitals and in the community. Virulence in S. aureus is mediated by an array of secreted and cell wall associated virulence factors, including toxins, hemolysins and proteases. In this work we identify a leucine aminopeptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S. aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a dramatic attenuation of virulence in both localized and systemic models of infection. LAP is required for survival inside human macrophages and gene expression analysis shows that pepZ expression is highest in the intracellular environment. We examine the cellular location of LAP and demonstrate that it is localized to the bacterial cytosol. These results identify for the first time an intracellular leucine aminopeptidase that influences disease causation in a Gram-positive bacterium.
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, 4202 East Fowler Ave, ISA2015 Tampa, FL 33620, USA.
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Robison
authors.forename: Frances E
authors.initials: FE
authors.lastname: Rivera
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Davenport
authors.forename: Ing-Marie
authors.initials: IM
authors.lastname: Jonsson
authors.forename: Danuta
authors.initials: D
authors.lastname: Florczyk
authors.forename: Andrej
authors.initials: A
authors.lastname: Tarkowski
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Joanna
authors.initials: J
authors.lastname: Koziel
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
mesh_terms: D000038:Abscess / Q000382:microbiology; D000818:Animals; D001170:Arthritis, Infectious / Q000382:microbiology; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002470:Cell Survival; D003600:Cytosol / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007931:Leucyl Aminopeptidase / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D007931:Leucyl Aminopeptidase