Metabolomics reveal potential natural substrates of AcrB in Escherichia coli and Salmonella enterica serovar Typhimurium

Wang-Kan, X; Rodríguez-Blanco, G; Southam, AD; Winder, CL; Dunn, WB; Ivens, A; Piddock, LJV

Journal article

Metabolomics reveal potential natural substrates of AcrB in Escherichia coli and Salmonella enterica serovar Typhimurium

Abstract:: In the fight against antibiotic resistance, drugs that target resistance mechanisms in bacteria can be used to restore the therapeutic effectiveness of antibiotics. The multidrug resistance efflux complex AcrAB-TolC is the most clinically relevant efflux pump in Enterobacterales and is a target for drug discovery. Inhibition of the pump protein AcrB allows the intracellular accumulation of a wide variety of antibiotics, effectively restoring their therapeutic potency. To facilitate the development of AcrB efflux inhibitors, it is desirable to discover the native substrates of the pump, as these could be chemically modified to become inhibitors. We analyzed the native substrate profile of AcrB in Escherichia coli MG1655 and Salmonella enterica serovar Typhimurium SL1344 using an untargeted metabolomics approach. We analyzed the endo- and exometabolome of the wild-type strain and their respective AcrB loss-of-function mutants (AcrB D408A) to determine the metabolites that are native substrates of AcrB. Although there is 95% homology between the AcrB proteins of S. Typhimurium and E. coli, we observed mostly different metabolic responses in the exometabolomes of the S. Typhimurium and E. coli AcrB D408A mutants relative to those in the wild type, potentially indicating a differential metabolic adaptation to the same mutation in these two species. Additionally, we uncovered metabolite classes that could be involved in virulence of S. Typhimurium and a potential natural substrate of AcrB common to both species.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Wang-Kan, X., Rodríguez-Blanco, G., Southam, A. D., Winder, C. L., Dunn, W. B., Ivens, A., & Piddock, L. J. V. (2021). Metabolomics reveal potential natural substrates of AcrB in Escherichia coli and Salmonella enterica serovar Typhimurium. MBio, 12(2).

MLA Style

Wang-Kan, X., et al. “Metabolomics Reveal Potential Natural Substrates of AcrB in Escherichia Coli and Salmonella Enterica Serovar Typhimurium.” MBio, vol. 12, no. 2, American Society for Microbiology , 2021.

Chicago Style

Wang-Kan, X, G Rodríguez-Blanco, AD Southam, CL Winder, WB Dunn, A Ivens, and LJV Piddock. 2021. “Metabolomics Reveal Potential Natural Substrates of AcrB in Escherichia Coli and Salmonella Enterica Serovar Typhimurium.” MBio 12 (2).
Share
Print