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Differences in gene usage dramatically change bacteria's 'lifestyles'

nella and E. coli share the gene for an antibiotic resistance regulatory protein called PmrA. By controlling when other proteins are produced, PmrA can make the cell wall more resistant to damage from the antibiotic polymyxin B. The PmrA protein normally activates in response to high iron levels.

In a paper recently published in Genes and Development, Groisman's lab established that another protein, PmrD, also can activate PmrA in response to low magnesium levels.

In the new study, Groisman's lab discovered that E. coli has a different version of PmrD that is unable to turn on the PmrA protein in response to low magnesium.

"We're not really sure what the significance of low magnesium is, but there are some indications that it may be important to the bacteria's ability to survive in white blood cells or outside of the host in soil or water," Groisman says.

When scientists transplanted the Salmonella form of PmrD into E. coli, the bacteria gained the ability to resist polymyxin B in low magnesium environments.

Based on data still to be published, Groisman suspects that many other aspects of microbial lifestyle are affected by differences in regulation of identical genes.

He notes that the idea of different organisms making altered use of the same genes sprang from recent analyses of the human genome.

"Humans not only appear to have far fewer genes than expected, there also seem to be fewer genes that are unique to human DNA than anticipated," Groisman explains.

In addition to instructions for building proteins, DNA contains stretches of code that affect when genes are turned on and off. As life becomes more complex over the course of evolution, Groisman explains, these regulatory sections appear to take up larger portions of the DNA, allowing genes to be turned on and off in ways that are more intricately responsive to the environment and other factors.

Human DNA, Groisman speculates, may be hea
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Contact: Michael Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
29-Nov-2004


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