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06 June 2010Science
Master regulators of Staph virulence revealed
Scientists have discovered a group of peptides produced by Staphylococcus aureus, including the drug-resistant strain MRSA, that are master regulators of many of the bugs’ virulence genes. If researchers could develop drugs that prevent the bacteria from making these peptides, called aureusamines, these drugs would be a welcome alternative to antibiotics. The scientists report their findings in the journal Science.
Because the aureusamines are “secondary metabolites,” meaning they aren’t essential to the bacteria’s survival, drugs that target these peptides might be less likely to cause resistant strains to evolve, as conventional antibiotics do. S. aureus causes infections via an array of toxins and virulence factors. One regulator of these virulence factors has already been discovered.
To look for others, Morgan Wyatt and colleagues took their cue from the first antibiotic developed for S. aureus infections. Penicillin is a secondary metabolite produced by fungi, and, unlike most peptides, it is produced by specialized enzymes independently of the ribosome. Wyatt and colleagues screened the S. aureus genome to look for genes that encoded a similar type of enzyme, which would also assemble nonribosomal secondary metabolites, in the bacterium itself.
They identified one such enzyme that assembles the aureusamines. These peptides proved to play an important role in establishing an infection, influencing the production of a variety of other virulence factors. Mice infected with a mutant strain unable to produce aureusamines experienced a much more limited infection compared to normal staph infections, the authors report.
M. A. Wyatt, W. Wang, C. M. Roux, F. C. Beasley, D. E. Heinrichs, P. M. Dunman, N.
A. Magarvey: Staphylococcus aureus Nonribosomal Peptide Secondary Metabolites Regulate Virulence. ScienceExpress, 3 June 2010, doi:10.1126/science.1188888
