September 4, 2018

“Resistance in the Wild: Understanding Where, When and Why Organisms Persist in the Wild” (2017)

Seed Grant in Pathogenic and Commensal Organisms

PIs are Siddhartha Thakur, Rob Dunn, and Matthew Koci, North Carolina State University. Despite major improvements in hygiene, quality of food and water, and advanced methods to detect antimicrobial resistant pathogens, these agents continue to pose a tremendous burden by them on public health agencies. By 2050, death due to infection by such resistant bacteria is predicted to be more common than due to cancer. In the standard telling, the problem of antibiotic resistance has simple causes. Doctors have overprescribed antibiotics for problems for which they are not suitable and farmers have overused antibiotics in animal feed in such a way as to both favor the origin of resistance and permit its maintenance. In this telling, the way forward to a world in which our antibiotics remain useful requires us “simply” to more sensibly manage the use of antibiotics. Of course, there is nothing simple about achieving such a goal, but at least in theory it seems conceptually possible and, in fact, some countries have both reduced use of antibiotics and, in doing so, reduced the prevalence of resistant bacteria in some settings, such as hospitals. A key component of this narrative is the idea that the plasmids that encode resistance are costly for bacteria to maintain. In the absence of antibiotics, those plasmids should become more rare (and the bacteria that have them, disadvantaged). Yet, one set of observations seems at odds with this narrative. Namely, resistant bacteria have, increasingly, been found in natural environments far from anthropogenic selective pressures that might favor their persistence. These anecdotes are now numerous and present a serious challenge to our understanding of antibiotic resistance. We seek to explore the possibility that some conditions in nature also favor the persistence of antibiotic resistance. Such conditions might both be important to understanding how to mitigate antibiotic resistance and useful for prediction the location of novel antibiotics.

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