Staphylococcus aureus genetic loci impacting growth and survival in multiple infection environments

Abstract

SummaryThe Gram-positive bacterium Staphylococcus aureus infects diverse tissues and causes a wide spectrum of diseases, suggesting that it possesses a repertoire of distinct molecular mechanisms promoting bacterial survival in disparate in vivo environments. Signaturetag transposon mutagenesis screening of a 1520-member library identified numerous S. aureus genetic loci affecting growth and survival in four complementary animal infection models including mouse abscess, bacteraemia and wound and rabbit endocarditis. Of a total of 237 in vivo attenuated mutants identified by the murine models, less than 10% showed attenuation in all three models, emphasizing the advantage of screening in diverse disease environments. The largest gene class identified by these analyses encoded peptide and amino acid transporters, some of which were important for S. aureus survival in all animal infection models tested. The identification of staphylococcal loci affecting growth, persistence and virulence in multiple tissue environments provides insight into the complexities of human infection and on the molecular mechanisms that could be targeted by new antibacterial therapies.

Staphylococcus aureus-Derived Staphopain B, a Potent Cysteine Protease Activator of Plasma Chemerin

“…Although SspB activity at S. aureus-infected sites has yet to be quantified, functional SspB is likely to be present within these lesions. Notably, inactivation of SspB and its processing enzyme, the V8 protease, results in attenuation of S. aureus virulence (18,33). Thus while chemerin processing by SspB may provide a host distress "SOS signal" to initiate pDC and/or macrophagemediated immunologic reactions, it is more likely to be an ongoing contributing factor to the pathological outcome of staphylococcal infections.…”

Structure of Coenzyme A−Disulfide Reductase from Staphylococcus aureus at 1.54 Å Resolution,

“…Reinforcing the concept that CoASH assumes the intracellular redox function of GSH in S. aureus, a novel NADPHdependent flavoprotein disulfide reductase, coenzyme A-disulfide reductase (CoADR 1 ), was identified (6,7). Consistent with the important functional role attributed to CoADR, staphylococcal virulence in mice was shown to be attenuated for CoADR-deficient strains (8,9).…”

Maturation of Lipoproteins by Type II Signal Peptidase Is Required for Phagosomal Escape of Listeria monocytogenes

“…In vivo screenings for attenuated mutants by signature-tagged mutagenesis, in Staphylococcus aureus, identified transposon insertions into the lsp gene (32,33). However, the effect of lsp inactivation on virulence was very modest.…”