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bioRxiv · 10.1101/2021.10.01.462822

A mycobacterial glycine-rich protein governs actin-based motility

Hill, N. S.·Welch, M. D.
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Abstract

Mycobacterium marinum, a close relative of the significant human pathogen Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. Here, we report the identification and characterization of MirA, the M. marinum actin-based motility factor. MirA is a member of the glycine-rich PE_PGRS family of ESX-5-secreted proteins. MirA uses an amphipathic helix to anchor into the mycobacterial outer membrane and, surprisingly, also the surface of host lipid droplet organelles. The glycine-rich PGRS domain in MirA directly binds and activates host N-WASP to stimulate actin polymerization through the Arp2/3 complex, directing both bacterial and lipid droplet actin- based motility. MirA is dissimilar to known N-WASP activating ligands and may represent a new class of microbial and host actin regulator. Additionally, the MirA-N-WASP interaction represents a model to understand how the enigmatic PE_PGRS proteins contribute to mycobacterial pathogenesis.

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Hill, N. S., Welch, M. D.. 2021-10-01. A mycobacterial glycine-rich protein governs actin-based motility. https://doi.org/10.1101/2021.10.01.462822

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