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Updated: Jun 2, 2025

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa
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In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa

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The mycomembrane differentially and heterogeneously restricts antibiotic permeation

Irene Lepori, Kiserian Jackson, Zichen Liu

    Biorxiv : the Preprint Server for Biology
    |January 13, 2025
    PubMed

    Insights

    The outer membrane of Mycobacterium tuberculosis is a selective barrier, not just impermeable. New research shows it differentially restricts antibiotic entry, impacting treatment strategies for tuberculosis.

    Area of Science:

    • Microbiology
    • Cell Biology
    • Drug Discovery

    Background:

    • The outer mycomembrane of Mycobacterium tuberculosis is widely considered a primary barrier to antibiotic treatment.
    • Previous evidence for mycomembrane impermeability relied on indirect or bulk population studies.

    Purpose of the Study:

    • To investigate the role of the mycobacterial mycomembrane as a selective barrier to small molecules.
    • To assess differential permeability of the mycomembrane to various compounds, including antibiotics.

    Main Methods:

    • Utilized the Peptidoglycan Accessibility Click-Mediated Assessment (PAC-MAN) method to trap molecules within the peptidoglycan layer of live mycobacteria.
    • Applied PAC-MAN to analyze the mycomembrane's restriction of fluorophores and antibiotic derivatives in both Mycobacterium tuberculosis and Mycobacterium smegmatis.

    Main Results:

    • The mycobacterial mycomembrane differentially restricts the entry of various fluorophores and antibiotic derivatives.
    • Discrimination was observed between different classes of antibiotics and even within the fluoroquinolone family.
    • Heterogeneous restriction of certain molecules, including vancomycin, was noted across sub-populations.

    Conclusions:

    • The mycobacterial mycomembrane acts as a selective barrier, controlling the permeation of specific molecules.
    • This cell-specific and molecule-specific barrier function has significant implications for developing effective tuberculosis therapies.

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