Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage...

Area of Science:

• Cell Biology
• Microbiology
• Immunology

Background:

• Intracellular pathogens like Mycobacterium tuberculosis invade host cells and damage phagosomal membranes to survive.
• The host's endosomal sorting complex required for transport (ESCRT) machinery repairs damaged endolysosomal membranes.
• M. tuberculosis utilizes the ESX-1 type VII secretion system (T7SS) to perforate phagosomes.

Purpose of the Study:

• To investigate if ESCRT machinery responds to pathogen-induced phagosomal damage.
• To determine if M. tuberculosis impairs the host's ESCRT-mediated membrane repair response.

Main Methods:

• Observing the recruitment of ESCRT-III proteins to M. tuberculosis-containing phagosomes.
• Analyzing the role of ESX-1 secretion system in ESCRT recruitment.
• Assessing the effect of M. tuberculosis effectors EsxG and EsxH on ESCRT-III recruitment and membrane repair.

Main Results:

• ESCRT-III proteins are recruited to M. tuberculosis phagosomes in an ESX-1-dependent manner.
• M. tuberculosis effectors EsxG and EsxH antagonize ESCRT-III recruitment to sites of membrane damage.
• EsxG and EsxH respond rapidly to membrane damage independently of ESCRT-III.

Conclusions:

• M. tuberculosis actively subverts the host's ESCRT-mediated membrane repair mechanisms.
• A molecular battle occurs between M. tuberculosis T7SS effectors and host ESCRT machinery over phagosome integrity.