Project Details
Projekt
Regulation of the AdeABC, AdeFGH, and AdeIJK efflux pumps in Acinetobacter baumannii
Applicant
Paul Higgins, Ph.D.
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
from 2014 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 258351992
The RND family of efflux pumps can contribute, and even be the cause of multidrug resistance when they are overexpressed in Acinetobacter baumannii. However, their overexpression is costly to the bacterium as they are energy dependent, therefore their regulation is tightly controlled. We have found that pump overexpression can be constitutive when the regulators are mutated or disrupted by IS elements. We have proven that the Asp20-Asn substitution in AdeR is the cause of AdeABC overexpression. However, we have also discovered that AdeRS, the two-component regulator of the efflux pump AdeABC, is not expressed when cells are grown on motility plates, suggesting the regulators are themselves regulated. Furthermore, under these conditions AdeABC is also not expressed. In this new proposal we aim to further characterise mutations in the genes encoding the regulators AdeRS and AdeN we have identified from our bioinformatics analysis of clinical isolates and their effect on AdeABC and AdeIJK expression, respectively, and also determine the resulting phenotype. Furthermore, we will characterise what we hypothesise to be important residues in AdeR we have identified through the crystal structure of AdeR. We also aim to determine using reporter systems what other pumps are differentially expressed under different growth conditions and the effect this has on the multidrug resistant phenotype.
DFG Programme
Research Units
Co-Investigator
Professor Harald Seifert
