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E. coli persists against antibiotics through HipA-induced dormancy
Date:1/15/2009

HOUSTON - Bacteria hunker down and survive antibiotic attack when a protein flips a chemical switch that throws them into a dormant state until treatment abates, researchers at The University of Texas M. D. Anderson Cancer Center report in the Jan.16 edition of Science.

"For antibiotics to work, bacteria have to be growing. Dormancy stops everything, allowing some bacteria to persist after treatment," said senior author Richard Brennan, Ph.D., professor in M. D. Anderson's Department of Biochemistry and Molecular Biology.

By demonstrating in detail how the HipA protein freezes bacterial activity, the researchers have opened the possibility of adding a new class of drugs to therapy against chronic and multidrug resistant bacterial infection.

Working in Escherichia coli, the team solved the structure of HipA and several of its protein complexes down to the atomic level, confirming that HipA is a protein kinase - an enzyme that works by transferring phosphate groups to its target molecules.

HipA is a type of protein kinase that is uncommon in bacteria, said lead author Maria Schumacher, Ph.D., associate professor of biochemistry and molecular biology. While other types of phosphorylation occur in bacteria, HipA phosphorylates proteins at their serine or threonine amino acids. This kinase activity is more commonly associated with eukaryotic cells, which make up animals, plants and fungi, and are generally thought to be more complex.

"These 'simple bacteria' are so complex. We're finding that life is sophisticated at all levels," Schumacher said. HipA is active in other types of gram-negative bacteria, which cause significant human bacterial infections.

Inhibitor could make persistent cells 'vanish'

A number of cancer drugs inhibit kinase activity in specific targets.

"If you stop HipA from working, there essentially is no persistence," Brennan said. "We need to see whether ki
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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