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Boston University biomedical engineers find chink in bacteria's armor
Date:9/6/2007

yl radical damage, you can potentiate or enhance the lethality of bactericidal antibiotics. This highlights the value of taking a network biology approach to antibiotics and provides a framework for creating new classes of drugs, said Collins.

What we think is happening is the cell is getting a signal that says, Theres something wrong with our energy production system and we need to make more energy. But, theres really nothing wrong. The cell becomes confused, turns on too many processes at once and its overwhelmed, said Kohanski.

Previous work by Kohanski and co-lead author Dan Dwyer, a postdoctoral researcher in Collins lab, revealed the first hints that this underlying pathway exists. In studying bacterial response to a quinolone, an antibiotic that inhibits DNA replication, they noted a surprising change in genes responsible for energy production and iron uptake.

In the current study, the researchers used DNA microarray studies to see if all three classes of bactericidal antibiotics triggered this process. Across the board, they noted increased gene activity along the intracellular assembly lines that make energy for the bacterial cell, just as in the earlier study. They began to deduce the details of the new pathway.

Cells produce free superoxide radicals naturally in oxygen-rich environments, but when they unnecessarily ramp up energy production to a frantic pace such as when triggered by antibiotics more radicals get churned out than the cells safety measures can mop up. The superoxide radicals then pull iron from other components of the cell, and this iron rapidly stimulates production of toxic levels of hydroxyl radicals.

Its really amazing that despite the diversity of targets, you have everything funneling into this common pathway, where theres a global meltdown occurring, said Dwyer. Theres almost no way for the cell to recover from this. It shows you how potent these molecules are to damaging and killi
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Contact: Mike Seele
mseele@bu.edu
617-353-9766
Boston University
Source:Eurekalert

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