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New route to identify drugs that can fight bacterial infections
Date:7/28/2014

isrupt the intracellular growth of four bacterial strains: Coxiella burnetii (which causes Q fever), Legionella pneumophila (Legionnaires' disease), Brucella abortus (brucellosis), and Rickettsia conorii (Mediterranean spotted fever). Although none of these organisms have become problem infections in the U.S. due to antibiotic resistance, brucellosis and Q fever can both cause chronic and ultimately fatal disease in about 5% of those infected.

The team screened each drug for its ability to reduce intracellular bacterial growth by 80% or more inside human THP-1 macrophage-like immune cells. They eliminated drugs from the list that simply killed off the human host cells or that were known antibiotic or antiviral drugs and identified 101 drugs that presumably disrupt key cellular functions in the host cells.

Shuman's lab group did the experiments on C. brunetii and L. pneumophila, while Sean Crosson's group at University of Chicago carried out the B. abortus work, and Juan Martinez's group, now at Louisiana State University in Baton Rouge, performed the R. conorii studies. The work, which was done at the Howard T. Ricketts Laboratory, a biocontainment laboratory operated by the University of Chicago in Lemont, Illinois, shows that known drugs that interfere with host cell properties can stall intracellular bacterial infections.

"There are emerging infections of all sortsbacteria, viruses, parasites. Working up a new therapy for such things take time," says Shuman. "If we have drugs X, Y, or Z to interfere with host cell functions to slow or impede an infection, then we can have something already on hand to attack it."


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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

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