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Reducing the Antibiotic Resistance Gene Reservoir by Plasmid Curing


<p>The long-term goal of this research is to decrease the reservoir of antibiotic resistance genes in food production animals by administration of bacterial plasmid curing compounds. This project will characterize in vitro plasmid curing activity of menthol and SDS on a well-characterized set of carbapenemase- and ESBL-producing Enterobacteriaceae. It will also determine whether administration of SDS and menthol can cure R-plasmids from ESBL-producing Enterobacteriaceae in mice.</p><p>Specific objectives:</p><p><ol><li>Quantify plasmid loss under varying levels of plasmid curing agents (menthol and SDS), temperature (room temperature and mammalian and avian body temperature), and bacterial density (low and high).</li><li> Co-culture R-plasmid carrying strains against R-plasmid cured counterparts to quantify differences in relative fitness.</li><li> Colonize germ-free mice with R-plasmid carrying strains of Enterobacteriaceae and treat with plasmid curing agents (menthol and SDS).</li><li> Quantify loss of R-plasmids in Enterobacteriaceae from mouse fecal pellets.</li><li> Remove plasmid curing agents and monitor bacterial population dynamics to understand the longer-term effects of plasmid curing agents. </li></ol></p>

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Once bacteria have become resistant to antibiotics, they do not lose this resistance easily. Certain chemicals already approved to be safe in humans and animals at low levels may increase the rate that bacteria lose antibiotic resistance. This benefit may outweigh the use of such chemicals in agriculture by making foods safer for human consumption. This project will test whether SDS and menthol, two chemical compounds currently present in a variety of human foods and cosmetics, can be used to make bacteria in animals more sensitive to antibiotics.

Walk, Seth
Montana State University
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