Fitness trade-offs of multidrug efflux pumps in < em > Escherichia coli < /em > K-12 in acid or base, and with aromatic phytochemicals

Appl Environ Microbiol. 2024 Jan 30:e0209623. doi: 10.1128/aem.02096-23. Online ahead of print.ABSTRACTMultidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log p...

Source: Applied and Environmental Microbiology - January 30, 2024 Category: Microbiology Authors: Yangyang Liu Andrew M Van Horn Minh T N Pham Bao Ngoc N Dinh Rachel Chen Slaybrina D R Raphael Alejandro Paulino Kavya Thaker Aaryan Somadder Dominick J Frost Chelsea C Menke Zachary C Slimak Joan L Slonczewski Source Type: research