An examination of the role of SpyA, an ADP-ribosyltransferase, in Streptococcus pyogenes pathogenesis.

摘要

Streptococcus pyogenes is a ubiquitous Gram-positive pathogen responsible for diseases that range in severity from minor skin and throat infections such as pharyngitis and impetigo, to life-threatening invasive infections such as meningitis, streptococcal toxic shock syndrome and necrotizing fasciitis. A C3-like ADP-ribosyltransferase produced by S. pyogenes was shown to target the eukaryotic proteins actin and vimentin. We begin to elucidate SpyA function by demonstrating that spyA-mutant bacteria cause smaller lesions in a mouse subcutaneous model of soft-tissue infection. Smaller lesion size is correlated with higher mRNA levels of the genes encoding the inflammatory chemokines CXCL1 and CCL2, in addition to the gene encoding vimentin. CXCL1, CCL2, and vimentin are important not only for phagocyte migration, but also for wound healing, suggesting that SpyA interferes with one of these processes to increase lesion size in wild type infected mice.;To further explore the role of SpyA in S. pyogenes infection, we developed transcriptional and translational fusions to the beta-glucuronidase reporter gene. The usefulness of our reporter fusions was verified by employing them to identify the spyA promoter region. In vitro infection of eukaryotic cells with a strain containing a transcriptional reporter fusion indicates that spyA transcription is induced during infection of murine macrophage-like cells, but not during infection of a human epithelial cell line, suggesting that SpyA's role in pathogenesis is most relevant to recruitment and activation of phagocytic cells.