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Updated: Nov 10, 2025

Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
Published on: January 5, 2024
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.
Abstract:
Mycobacterium abscessus is a pulmonary pathogen that exhibits intrinsic resistance to antibiotics, but the factors driving this resistance are incompletely understood. Insufficient intracellular drug accumulation could explain broad-spectrum resistance, but whether antibiotics fail to accumulate in M. abscessus and the mechanisms required for drug exclusion remain poorly understood. We measured antibiotic accumulation in M. abscessus using mass spectrometry and found a wide range of drug accumulation across clinically relevant antibiotics. Of these compounds, linezolid accumulates the least, suggesting that inadequate uptake impacts its efficacy. We utilized transposon mutagenesis screening to identify genes that cause linezolid resistance and found multiple transporters that promote membrane permeability or efflux, including an uncharacterized protein that effluxes linezolid and several chemically related antibiotics. This demonstrates that membrane permeability and drug efflux are critical mechanisms of antibiotic resistance in M. abscessus and suggests that targeting membrane transporters could potentiate the efficacy of certain antibiotics.
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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