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Updated: Oct 18, 2025

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
05:06

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

Published on: January 5, 2024

792

Structure of the Acinetobacter baumannii PmrA receiver domain and insights into clinical mutants affecting DNA

Samantha Palethorpe, Morgan E Milton, Everett C Pesci

    Journal of Biochemistry
    |September 29, 2021
    PubMed

    Insights

    Acinetobacter baumannii PmrA protein mutations enhance colistin resistance. Understanding these PmrA structural changes helps develop new antimicrobial therapies against this nosocomial pathogen.

    Area of Science:

    • Microbiology
    • Molecular Biology
    • Structural Biology

    Background:

    • Acinetobacter baumannii is a critical nosocomial pathogen with emerging resistance to colistin, a last-resort antibiotic.
    • Colistin resistance is frequently linked to mutations in the PmrAB two-component regulatory system.
    • Understanding the PmrAB system's regulation is crucial for combating antibiotic resistance.

    Purpose of the Study:

    • To biochemically characterize the Acinetobacter baumannii PmrA response regulator.
    • To elucidate the DNA-binding motif and regulon of the A. baumannii PmrAB system.
    • To determine the structural basis of colistin resistance conferred by PmrA mutations.

    Main Methods:

    • Biochemical characterization of Acinetobacter baumannii PmrA.
    • DNA-binding analysis using the Klebsiella pneumoniae PmrA box motif.
    • X-ray crystallography for N-terminal domain structure determination.
    • Molecular modeling for full-length PmrA structure and mutation analysis.

    Main Results:

    • A. baumannii PmrA binds to a specific DNA motif (5'-HTTAAD N5 HTTAAD).
    • The first structural information of the A. baumannii PmrA N-terminal domain was obtained.
    • Two mutations (PmrA::I13M and PmrA::P102R) were identified to confer increased colistin resistance.
    • Structural and dynamic insights into how these mutations affect PmrA function were inferred.

    Conclusions:

    • The PmrAB system plays a key role in Acinetobacter baumannii colistin resistance.
    • Structural and functional characterization of PmrA provides a basis for understanding resistance mechanisms.
    • These findings can guide the development of novel antimicrobial strategies against resistant A. baumannii.
    Keywords:
    Acinetobacter baumanniiPmrAcolistin resistanceresponse regulatortwo-component system

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