Researchers have identified two genes that represent potential new drug targets for combating MRSA. The copper- and sulfur-binding repressors they encode are similar to molecules already identified in other bacteria, including Mycobacterium tuberculosis. The Indiana University-led research is published in the Journal of Biological Chemistry, in a paper titled, “Control of Copper Resistance and Inorganic Sulfur Metabolism by Paralogous Regulators in Staphylococcus aureus.”
All strains of Staphylococcus aureus encode a putative copper-sensitive operon repressor (CsoR) and one other CsoR-like protein of unknown function, explains Indiana University’s David Giedroc, Ph.D., and Vanderbilt School of Medicine’s Erik Sakaar, Ph.D., who spearheaded the research. Funded in part by an NIH grant, the team looked further at the two genes in S. aureus, to investigate their activity in the bacterial cells. They found the CsoR regulates the expression of copper resistance genes, and the molecule is related to a CsoR previously discovered by Dr. Giedroc’s group in Mycobacteriam tuberculosis. The other repressor, termed CstR (CsoR-like sulfurtransferase repressor), appears to react with various forms of sulfur and prevents the transcription of a series of genes that, based on their homology with genes in other bacteria, are involved in sulfur assimilation.
The researchers suggest that while the CsoR and CstR genes themselves could represent new MRSA drug targets, the genes they regulate are probably a more likely source of targets. “I think the repressors are one step removed from where you’d like to have the action,” professor Giedroc remarks. “At this point I think the better targets are going to be the genes they are regulating.”
Promisingly, the metabolic process by which sulfur is assimilated in Mycobacterium tuberculosis is already a proven target for this bacterium, he adds. “We see no reason why this can’t be the case for Staphylococcus aureus.” The NIH has now awarded professor Goedric’s lab another $1.1 million to fund further investigations into how S. aureus utilizes sulfur.