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Douglas Mitchell: Do Bad Bugs Have Off Switches?


Recommended by: Gene Robinson, University of Illinois at Urbana-Champaign

Outbreaks of deadly drug-resistant pathogens are becoming more commonplace as antibiotics are overused and their potency decays.

Doug Mitchell loves antibiotics, but he says there must be a better way to treat disease. The University of Illinois at Urbana-Champaign's Mitchell is trying to develop new targets to create drugs that do not kill pathogens, but disrupt their ability to produce toxins, all without affecting the beneficial microbes in the body.

His lab is focused on toxin biosynthesis, and on "understanding its mechanistic enzymology, and then devising a strategy to disrupt it." To do so, the Mitchell lab is using a genome mining and reconstitution approach to identify compounds and agents that are selective for these pathogenic mechanisms.

"The more we learn about how these enzymes that produce architecturally complex toxins function, the better we can then design specific inhibitors or set up screens to find compounds that block the ability for bugs to make those toxins," he says.

Looking ahead

As he pursues this new approach to battling pathogens, probably the largest hurdle Mitchell faces is finding ways to get these new compounds tested in animal models.

"You might ask yourself the question: Why can't we have smarter antibiotics right now? Why can't your antibiotics currently distinguish between friend and foe in the body?" he says. "Probably the reason for that is the way that we currently discover antibiotics."

In spite of the built-in difficulty of creating new ways to undermine the effect of bad bugs in the human body, Mitchell has some specific milestone he'd like to see. "In five years, I'd like to have five new agents out there that are specific for five different pathogens. I'd like to have published on five new disease areas and have five new compounds that are specific to those pathogens," he says. "That's a pretty lofty goal. But it would be a good place to set the bar."

His team is already making progress on Streptococcus pyogenes, which causes strep throat, toxic shock syndrome, and other diseases, and it is working on compounds that may work against Listeria monocytogenes, a foodborne pathogen that causes listeriosis, and compounds that could inhibit diseases such as meningitis and gonorrhea.

And the Nobel goes to...

"It's a career goal of mine ... to contribute to the eradication of infectious disease," Mitchell says, adding that "if this lab and other labs around the world are able to come up with new strategies to make antibiotics better, to come up with new ways of vaccinating people, to make bacterial infections a thing of the past, that is what I would want to make a contribution to."

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