New Therapeutic Targets for Drug-resistant Staph Infections

Scientists have discovered two genes that encode copper and sulfur-binding repressors in the Staphylococcus aureus, which they say could provide two new potential avenues for controlling the increasingly drug-resistant bacterium.

"Staph is becoming more and more multi-drug resistant, and both of the systems we discovered are promising," said Indiana University Bloomington biochemist David Giedroc, who led the project.

New Target To Fight Cholesterol And Staph Infection
Researchers have zeroed in on a possible target to lower cholesterol and fight staph infection.

iedroc's team collaborated with Vanderbilt University School of Medicine infectious disease specialist Eric Skaar and University of Georgia chemist Robert Scott for the study.

One of the repressors the scientists discovered, CsoR (Copper-sensitive operon Repressor), regulates the expression of copper resistance genes, and is related to a CsoR, the bacterium that causes tuberculosis in humans.

When the bacterium is exposed to excess copper, the repressor binds copper (I) and falls away from the bacterial genome to which it is bound, making it possible for the copper resistance genes to be turned on.

Drinking Cranberry Juice Can Block Staph Infections
Making a surprising discovery, researchers at Worcester Polytechnic Institute (WPI) have found that cranberry juice cocktail blocked a strain of Staphylococcus aureus (S.

This makes sense, since in the presence of a lot of copper-a metal commonly used to kill bacteria-a bacterium is well served by expressing genes that help the bacterium sequester and export extra copper before the metal can do any real damage.

The other repressor, CstR (CsoR-like sulfurtransferase Repressor), which the scientists found can react with various forms of sulfur, appears to prevent the transcription of a series of sulfur assimilation genes based on their homology with similar genes in other bacterial species.

Deadly Staph Infections Fought Well With Antibiotics Combo
An international team of researchers has found that a combination of two antibiotics is effective in fighting pathogenic bacteria.

One of the genes in this system encodes a well-known enzyme, sulfurtransferase, which interconverts sulfite (SO3 2-) and thiosulfate, (S2O3 2-).

The two repressors and the gene systems they regulate are possible new drug targets for controlling Staph growth.

US Sees Rise in Drug-Resistant Staph Infections
Cases of antibiotic-resistant staph infections usually acquired in the community are growing in the United States and rapidly spreading to hospitals, researchers said Tuesday.

A drug could hypothetically target either of the repressors, causing bacteria to become unresponsive to toxic copper levels or incapable of properly integrating sulfur into their cell physiologies, respectively.

"One thing you could do is prevent the repressors from coming off the DNA in the first place although I think that's probably a long shot," said Giedroc.

"I think the repressors are one step removed from where you'd like to have the action. At this point I think the better targets are going to be the genes they are regulating," he said.

Among those genes, Giedroc said he's hopeful one of the sulfur utilization genes controlled by CstR turns out to be an effective drug target.

The study will appear in the April 15, 2011 issue of the Journal of Biological Chemistry.

Source-ANI