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Researchers find novel way to fight antibiotic resistance

Kathleen Blanchard's picture
Brown University researchers have a new way of attacking antibiotic resistance.

Brown University chemists have developed a compound that can fight antibiotic resistance. The novel weapon is known as BU-005 that makes old antibiotics become potent again.

The scientists explain BU-005 attacks bacteria by blocking proteins in the cell membrane of bacteria.

BU-005 U-005 that belongs to a family of C-capped dipeptides blocks efflux pumps that are employed by bacteria to resist antibacterial agents called chloramphenicol.

The researchers found if they block the efflux pumps with the C-capped peptides they can restore the potency of old antibiotics to fight diseases like MRSA and tuberculosis.

Jason Sello, assistant professor of chemistry at Brown University explains, “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.

“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.”

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Sello explains a bacterium can go from being susceptible to antibiotics to resistant to five or six antibacterials by acquiring a single gene.

A company called MPEX Pharmaceuticals recently tested C-capped peptides on Gram negative bacteria, some of which include Acinobacter and E. coli. One of the MPEX drugs made it to a phase I clinical trial.

Sello and his team developed BU-500 after exploring and testing nearly 100 C-capped dipeptides that are effective against both Gram negative and Gram positive bacteria.

“Our findings that C-capped dipeptides inhibit efflux pumps in both Gram-positive and Gram-negative bacteria should reinvigorate interest in these compounds," Sello said. "Moreover, our simplified synthetic route should make the medicinal chemistry on this class of compounds much simpler.”

Attacking bacteria by inhibiting efflux pumps could offer a new approach to fight antibiotic resistance. Results of the study appear in Bioorganic and Medicinal Chemistry.

Bioorganic and Medicinal Chemistry: doi:10.1016/j.bmc.2011.10.011
“Synthesis and evaluation of inhibitors of bacterial drug efflux pumps of the major facilitator superfamily”
Babajide O. Okandeji et al.
December, 2011

Image Credit: Brown University