Document Detail


Poly-N-acetylglucosamine production in Staphylococcus aureus is essential for virulence in murine models of systemic infection.
MedLine Citation:
PMID:  16177366     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The contribution of the Staphylococcus aureus surface polysaccharide poly-N-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (ica) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA-deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.
Authors:
Andrea Kropec; Tomas Maira-Litran; Kimberly K Jefferson; Martha Grout; Sarah E Cramton; Friedrich Götz; Donald A Goldmann; Gerald B Pier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Infection and immunity     Volume:  73     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-22     Completed Date:  2005-11-28     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6868-76     Citation Subset:  IM    
Affiliation:
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adhesins, Bacterial / genetics
Animals
Bacteremia / immunology,  microbiology*
Bacterial Proteins / genetics*
Disease Models, Animal
Gene Deletion
Immunity, Innate / immunology
Mice
Phagocytosis
Staphylococcal Infections / immunology,  microbiology*
Staphylococcus aureus / genetics,  metabolism,  pathogenicity*
Virulence / genetics
beta-Glucans / chemistry,  immunology*
Grant Support
ID/Acronym/Agency:
AI061590/AI/NIAID NIH HHS; AI46706/AI/NIAID NIH HHS; R01 AI046706/AI/NIAID NIH HHS; R01 AI046706-05/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adhesins, Bacterial; 0/Bacterial Proteins; 0/SarA protein, Staphylococcus aureus; 0/adhesin, Staphylococcus aureus; 0/beta-Glucans; 0/poly-N-acetyl-1-6-glucosamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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