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A drug used to treat HIV might defuse deadly staph infections
Date:12/14/2012

after Dr. Torres asked Dr. Unutmaz and fellow HIV researcher Nathaniel Landau, PhD, professor of microbiology, if he might use some of the human immune cells they had collected over the course of their HIV studies. The laboratories of all three scientists are adjacent to each other. Dr. Torres was trying to find out which immune cells were affected by different leukotoxins. Dr. Unutmaz gave him a T cell line, which they were using for their HIV infection studies and had previously engineered to express CCR5, to test the effects of these toxins.

"Within one hour flat, T cells with CCR5 all died when exposed to LukED" says Dr. Torres, whereas a similar T cell line that lacked the receptor was completely resistant to the toxin's effects. This observation quickly led to another set of experiments to determine that the LukED toxin was indeed interacting with the receptor and that its presence on the cell surface was necessary for the toxin to kill the cells.

The investigators then treated cells with CCR5 with maraviroc, a drug on the market that binds to CCR5 and blocks HIV infection, and then exposed the cells to the Staph toxin. The result, the scientists say, was astonishing. "It was remarkable. Maraviroc completely blocked the toxic effects of this leukotoxin at doses similar to those used to inhibit HIV infection" Dr. Unutmaz says.

"The goal in blocking the toxin with maraviroc or similar agents is to give the upper hand to the immune system to better control the infection," Dr. Torres adds. The researchers further corroborated the critical role of CCR5 in Staph infections using a mouse model. When they infected mice susceptible to Staph infection with strains that contain the LukED toxin, almost all the mice died. However, mice that were genetically engineered to lack CCR5 on their cells survived this lethal Staph infection.

Based on these findings, the investigators hope that future human clinical trials will determine wh
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Contact: Christopher Rucas
Christopher.Rucas@nyumc.org
212-404-3525
NYU Langone Medical Center / New York University School of Medicine
Source:Eurekalert

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