"We need to come up with new targets for antibacterial agents," said Indiana University Bloomington biochemist David Giedroc, who led the project. "Staph is becoming more and more multi-drug resistant, and both of the systems we discovered are promising."
The work was a collaboration of members of Giedroc's laboratory, and that of Vanderbilt University School of Medicine infectious disease specialist Eric Skaar, and University of Georgia chemist Robert Scott.
MRSA, or multidrug-resistant Staphylococcus aureus, is the primary cause of nosocomial infections in the United States. About 350,000 infections were reported last year, about 20 percent of which resulted in fatalities, according to the Centers for Disease Control. One to two percent of the U.S. population has MRSA in their noses, a preferred colonization spot.
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 previously discovered by the Giedroc group in Mycobacterium tuberculosis, 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. 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. One of the genes in this system encodes a well known enzyme, sulfurtransferase, which interconverts sulfite (SO3 2-) and thiosulfate, (S2O3 2-).
The scientists have yet to confirm the functions of the other genes controlled by CstR, but a new four-year, $1.1 million grant from the National Institutes of Health to principal investigator Giedroc will fund crucial investigations into Staph's utilization of sulfur, an important element that bacteria -- and all organisms for that matter -- use to make protein.
The two repressors -- and the gene systems they regulate -- are possible new drug targets for controlling Staph growth. 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," Giedroc said "although I think that's probably a long shot. 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."
Among those genes, Giedroc says he's hopeful one of the sulfur utilization genes controlled by CstR turns out to be an effective drug target. And he wouldn't be surprised if that was the case.
"The metabolic process by which sulfur is assimilated is a proven drug target in Mycobacterium tuberculosis," Giedroc said. "We see no reason why this can't be the case for Staphylococcus aureus. Finding out will be one of the goals of this new NIH-funded project."
Nicholas Grossoehme and Zhen Ma of IU Bloomington, Thomas Kehl-Fie and Keith Adams of Vanderbilt, and Darin Cowart of Georgia also contributed to the report. The project was funded by grants from the National Institutes of Health, the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense, and the American Heart Association.
To speak with Giedroc, please contact David Bricker, University Communications, at 812-856-9035 or email@example.com.
David Bricker | EurekAlert!
Aquaculture: Clear Water Thanks to Cork
28.10.2016 | Technologie Lizenz-Büro (TLB) der Baden-Württembergischen Hochschulen GmbH
Bioluminescent sensor causes brain cells to glow in the dark
28.10.2016 | Vanderbilt University
Physicists from the University of Würzburg have designed a light source that emits photon pairs. Two-photon sources are particularly well suited for tap-proof data encryption. The experiment's key ingredients: a semiconductor crystal and some sticky tape.
So-called monolayers are at the heart of the research activities. These "super materials" (as the prestigious science magazine "Nature" puts it) have been...
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
28.10.2016 | Power and Electrical Engineering
28.10.2016 | Life Sciences
28.10.2016 | Life Sciences