<i>Staphylococcus aureus</i> Nonribosomal Peptide Secondary Metabolites Regulate Virulence

Golden Regulator Staphylococcus aureus is a common cause of intractable infections that are exacerbated by an array of toxins and virulence factors. The agr pheromone has been thought to represent the master regulator of virulence in this pathogen, but it is not always expressed and is also found in many nonpathogenic cocci. A strictly conserved, nonribosomal peptide synthetase has now been found by Wyatt et al. (p. 294 , published online 3 June) by genome mining. The enzyme assembles valine and tyrosine into cyclic dipeptides called aureusimines that are expressed by all sequenced strains of S. aureus , including the “superbug” MRSA (Methicillin-resistant Staphylococcus aureus ). Microarray analysis showed a striking effect of mutation in the synthetase locus on the production of immunomodulators, hemolysins, and other exotoxins by the pathogen. Indeed, mice infected systemically with the mutant strain showed a restricted spread of infection compared with the wild type.

Staphylococcus aureus Nonribosomal Peptide Secondary Metabolites Regulate Virulence Journal Articles