title: The lone S41 family C-terminal processing protease in Staphylococcus aureus is localized to the cell wall and contributes to virulence.
abstract: Staphylococcus aureus is a versatile pathogen of humans and a continued public health concern due to the rise and spread of multidrug-resistant strains. As part of an ongoing investigation into the pathogenic mechanisms of this organism we previously demonstrated that an intracellular N-terminal processing protease is required for S. aureus virulence. Following on from this, here we examine the role of CtpA, the lone C-terminal processing protease of S. aureus. CtpA, a member of the S41 family, is a serine protease whose homologues in Gram-negative bacteria have been implicated in a range of biological functions, including pathogenesis. We demonstrate that S. aureus CtpA is localized to the bacterial cell wall and expression of the ctpA gene is maximal upon exposure to conditions encountered during infection. Disruption of the ctpA gene leads to decreased heat tolerance and increased sensitivity when exposed to components of the host immune system. Finally we demonstrate that the ctpA(-) mutant strain is attenuated for virulence in a murine model of infection. Our results represent the first characterization of a C-terminal processing protease in a pathogenic Gram-positive bacterium and show that it plays a critical role during infection.
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Rivera
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Courtney K
authors.initials: CK
authors.lastname: Cavaco
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Johnson
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Martin
authors.affiliation: Department of Cell Biology, Microbiology & Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000201:enzymology* / Q000235:genetics; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D021381:Protein Transport; D016415:Sequence Alignment; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D010450:Endopeptidases; C072135:C-terminal processing peptidase