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Staphylococcus aureus is a global pathogen, responsible for an array of different illnesses in humans and animals. In particular, community-associated methicillin-resistant S. aureus (CA-MRSA) strains of the pandemic USA300 clone have the capacity to cause lethal human necrotizing pneumonia, but the molecular basis for the enhanced virulence remains unclear. Bacterial superantigens (SAg) stimulate T-cell hyper-activation resulting in severe systemic illnesses such as toxic shock syndrome (TSS). However, all S. aureus SAgs identified to date are encoded by mobile genetic elements found only in a proportion of clinical isolates. Here, we report the discovery of a unique core genome-encoded SAg (SElX) which was acquired by an ancestor of the S. aureus species and which has undergone genetic and functional diversification in pathogenic clones infecting humans and animals. Importantly, we report that SElX made by pandemic USA300 contributes to lethality in a rabbit model of human necrotizing pneumonia revealing a novel virulence determinant of severe CA-MRSA infection.
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