Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in Mycobacterium abscessus

Kerry McGowen1, Tobias Funck1,2, Xin Wang1

  • 1Department of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Plos Pathogens
|April 10, 2025
PubMed

Insights

Mycobacterium abscessus resists antibiotics due to poor drug accumulation and efflux. Identifying transporters involved in excluding drugs like linezolid could improve treatment efficacy.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Drug Resistance

Background:

  • Mycobacterium abscessus is a significant pulmonary pathogen known for its intrinsic antibiotic resistance.
  • The precise mechanisms underlying this broad-spectrum resistance, particularly concerning intracellular drug accumulation, are not fully elucidated.

Purpose of the Study:

  • To investigate antibiotic accumulation in Mycobacterium abscessus.
  • To identify the genetic factors and mechanisms responsible for antibiotic resistance, focusing on drug efflux and membrane transport.

Main Methods:

  • Quantitative measurement of antibiotic accumulation in M. abscessus using mass spectrometry.
  • Transposon mutagenesis screening to identify genes conferring resistance to linezolid.

Main Results:

  • Significant variation in antibiotic accumulation was observed across different drugs.
  • Linezolid showed the lowest accumulation, indicating potential drug exclusion mechanisms.
  • Identification of multiple transporters involved in membrane permeability and drug efflux, including a novel protein effluxing linezolid and related antibiotics.

Conclusions:

  • Membrane permeability and active drug efflux are critical determinants of antibiotic resistance in M. abscessus.
  • Targeting these identified membrane transporters may represent a viable strategy to enhance the efficacy of existing antibiotics against this pathogen.

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