title: XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr-Dependent and agr-Independent Pathways.
abstract: We demonstrate that mutation of xerC, which reportedly encodes a homologue of an Escherichia coli recombinase, limits biofilm formation in the methicillin-resistant Staphylococcus aureus strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1xerC mutant and undetectable in both LAC and its isogenic xerC mutant. Mutation of xerC also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic xerC mutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilm in vivo. Mutation of xerC also attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest that xerC may impact the functional status of agr. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1xerC mutants. However, this cannot account for the biofilm-deficient phenotype of xerC mutants because mutation of agr did not limit biofilm formation in either strain. These results demonstrate that xerC contributes to biofilm-associated infections and acute bacteremia and that this is likely due to agr-independent and -dependent pathways, respectively.
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Danielle N
authors: http://orcid.org/0000-0002-9106-3386
authors: DN
authors: Atwood
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Karen E
authors: KE
authors: Beenken
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Allister J
authors: AJ
authors: Loughran
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Daniel G
authors: DG
authors: Meeker
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Tamara L
authors: TL
authors: Lantz
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Justin W
authors: JW
authors: Graham
authors: Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Horace J
authors: HJ
authors: Spencer
authors: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA smeltzermarks@uams.edu.|Department of Orthopedic Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.|Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors: Mark S
authors: MS
authors: Smeltzer
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009876:Operon; D010456:Peptides, Cyclic / Q000235:genetics / Q000378:metabolism*; D045522:Recombinases / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism
chemical_list: C414532:AgrD protein, Staphylococcus; D001426:Bacterial Proteins; D010456:Peptides, Cyclic; D045522:Recombinases