Mycobacterium tuberculosis Type VII Secreted Effector EsxH Targets Host ESCRT to Impair Trafficking

• DOI: 10.1371/journal.ppat.1003734
• Publication Date: 2013-11-01T03:12:20Z
• Authors: Alka Mehra; Aleena Zahra; Victor Thompson; Natalie Sirisaeng...; Ashley Wells; Maura Porto; Stefan Köster; Kristen Penberthy; Yoshihisha Kubota; Amelie Dricot; Daniel Rogan; Marc Vidal; David E. Hill; Andrew J. Bean; Jennifer A. Philips
• Keywords: ESCRT; Phagolysosome

Mycobacterium tuberculosis (Mtb) disrupts anti-microbial pathways of macrophages, cells that normally kill bacteria. Over 40 years ago, D'Arcy Hart showed Mtb avoids delivery to lysosomes, but the molecular mechanisms allow elude lysosomal degradation are poorly understood. Specialized secretion systems often used by bacterial pathogens translocate effectors target host, and encodes type VII (TSSSs) enable mycobacteria secrete proteins across their complex cell envelope; however, cellular targets unknown. Here, we describe a systematic strategy identify virulence factors looking for interactions between secretome host using high throughput, stringency, yeast two-hybrid (Y2H) platform. Using this approach identified an interaction EsxH, which is secreted Esx-3 TSSS, human hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), component endosomal sorting required transport (ESCRT). ESCRT has well-described role in directing destined into intraluminal vesicles (ILVs) multivesicular bodies (MVBs), ensuring sorted cargo upon MVB-lysosome fusion. show deliver lysosome restrict intracellular growth. Further, with EsxG, function impairs phagosome maturation. Thus, demonstrate TSSS machinery one central features pathogenesis.