Extreme Acid Modulates Fitness Trade-Offs of Multidrug Efflux Pumps MdtEF-TolC and AcrAB-TolC in Escherichia coli K-12
Samantha H. Schaffner, Abigail V. Lee, M.T. Pham, Beimnet B. Kassaye, Haofan Li, Sheetal Tallada, Cassandra Lis, Mark L. Lang, Yangyang Liu, Nafeez Ahmed, Logan G. Galbraith, Jeremy P. Moore, Katarina M. Bischof, Chelsea C. Menke, Joan L. Slonczewski
Abstract
Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump that otherwise incurs a fitness cost. At the same time, extreme acid amplifies the effect of salicylate selection against multidrug pumps. Thus, organic acids and stomach acid could play important roles in regulating multidrug resistance in the gut microbiome. Our flow cytometry assay provides a way to measure the fitness effects of extreme-acid exposure to various membrane-soluble organic acids, including plant-derived nutrients and pharmaceutical agents. Therapeutic acids might be devised to control the prevalence of multidrug pumps in environmental and host-associated habitats.