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Related Experiment Video

Updated: Feb 13, 2026

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pH-responsive substrate switching in mycobacterial Type VII ESX secretion.

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    Pathogenic mycobacteria, like Mycobacterium marinum, adapt their virulence factor secretion (ESX-1 substrate switching) in response to acidic environments within host cells, aiding infection.

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    Area of Science:

    • Microbiology
    • Pathogenesis
    • Host-pathogen interactions

    Background:

    • Pathogenic mycobacteria, including those causing tuberculosis, reside within host macrophages.
    • The ESX-1 secretion system (early secreted antigen 6 kilodaltons system-1) is crucial for mycobacterial virulence, enabling phagosome lysis and host cell invasion.
    • The mechanisms by which ESX-1 functions in diverse intracellular environments are not fully understood.

    Purpose of the Study:

    • To investigate how the ESX-1 secretion system adapts its function in response to environmental cues, specifically pH.
    • To elucidate the molecular mechanisms underlying ESX-1 substrate switching.
    • To determine the role of ESX-1 substrate switching in mycobacterial infection models.

    Main Methods:

    • Culturing *Mycobacterium marinum* in acidic conditions *in vitro* to observe substrate switching.
    • Analyzing changes in ESX-1 substrate transcript levels via gene expression analysis.
    • Quantifying ESX-1 substrate and chaperone protein levels using proteomic techniques.
    • Evaluating the requirement of specific ESX-1 substrates in an acidic infection model *in vivo*.

    Main Results:

    • *Mycobacterium marinum* exhibits ESX-1 substrate switching when grown at acidic pH *in vitro*.
    • Substrate switching is associated with significant alterations in ESX-1 substrate transcript and protein levels, as well as chaperone levels.
    • Specific ESX-1 transcripts are upregulated *in vivo*, and distinct substrate sets are necessary for infection in an acidic environment.

    Conclusions:

    • The ESX-1 secretion system dynamically switches its secreted substrates in response to environmental acidity.
    • This substrate switching is regulated at both the transcript and protein levels.
    • Mycobacterial pathogens likely utilize distinct ESX-1 protein sets to lyse macrophage phagosomes of varying acidity during infection, contributing to pathogenesis.