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New compound defeats drug-resistant bacteria
Date:11/28/2011

PROVIDENCE, R.I. [Brown University] It's no wonder that medicine's effort to combat bacterial infections is often described as an arms race. When new drugs are developed to combat infections, the bacterial target invariably comes up with a deterrent.

A particularly ingenious weapon in the bacterial arsenal is the drug efflux pump. These pumps are proteins located in the membranes of bacteria that can recognize and expel drugs that have breached the membranes. In some cases, the bacterial pumps have become so advanced they can recognize and expel drugs with completely different structures and mechanisms.

"This turns out to be a real problem in clinical settings, especially when a bacterial pathogen acquires a gene encoding an efflux pump that acts on multiple antibiotics," said Jason Sello, assistant professor of chemistry at Brown University. "In the worst case scenario, a bacterium can go from being drug-susceptible to resistant to five or six different drugs by acquiring a single gene."

"That leaves two choices: Make more new and costly antibiotics or find a way around the pump. Sello and his group chose the latter. In a paper published in the journal Bioorganic and Medicinal Chemistry, the team reports it has discovered a new compound of C-capped dipeptides, called BU-005, to circumvent a family of drug-efflux pumps associated with Gram-positive bacteria, which include the dangerous MRSA and tuberculosis strains. Until that discovery, C-capped dipeptides were known to work only against an efflux pump family associated with Gram-negative bacteria.

"If drug efflux pumps are inhibited, then bacteria will be susceptible to drugs again," Sello said. "This approach is of interest because one would have to discover efflux pump inhibitors rather than entirely new kinds of antibacterial drugs."

Recently, a company called MPEX Pharmaceuticals discovered that specific C-capped dipeptides could block the efflux pu
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Contact: Richard Lewis
Richard_Lewis@brown.edu
401-863-3766
Brown University
Source:Eurekalert  

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