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Research sheds light on Staphylococcus aureus virulence
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A group of nonribosomal peptide secondary metabolites, called aureusimines, plays a key role in the virulence of Staphylococcus aureus, according to a study.
Researchers from McMaster University in Ontario used a genome mining approach to predict nonribosomal peptides that are exclusive and highly preserved within S. aureus. They looked for genes that encoded a similar type of enzyme that would also assemble nonribosomal secondary metabolites.
The researchers noted that two nonribosomal peptide secondary metabolites, the aureusimines, act as regulators of the disease’s pathogenicity and are necessary to produce further infections. Two groups of mice were used to test the aureusimines. One group was injected with a mutant strain of S. aureus and the other was injected with the normal strain. The mouse models showed that strains of S. aureus that were unable to produce the aureusimines were thinned and/or cleared from major organs.
Also, these strains of MRSA had tamed and were unable to burst open red blood cells, which left it non-functional and non-infectious. The discovery provides new options for treatment and disabling the powerful bacteria. Since the aureusimines are secondary metabolites and are not essential to the bacteria’s survival, medications that target these peptides might be less likely to become resistant as strains evolve.
Wyatt et al have discovered that Staphylococcus aureus produces two nonribosomal peptide secondary metabolites (they have named them aureusimines A&B) that regulate expression of several virulence factors including the genes encoding chemotaxis-inhibitory protein, fibrinogen-binding protein, fibronectin-binding protein, and hemolysins. In mouse experiments with a laboratory strain (Newman) versus an isogenic mutant lacking the gene encoding for aureusimine , the mutant strain was less infective. The investigators used a molecular approach for predicting this previously unknown class of staphylococcal metabolites and propose that they offer a novel target for anti-infective agents. The findings are of interest and a first step in discovery of potentially important regulators of virulence in this pathogen. How these findings relate to infections in humans with community or healthcare associated S. aureus infections remains to be determined but development of novel antimicrobial agents to combat antibiotic resistant S. aureus infections is a definite priority.
– Sheldon K. Kaplan, MD
Infectious
Diseases in Children Editorial Board