TY - JOUR T1 - The ESX-1 secretion system senses bacterial contact and prepares mycobacteria for environmental adaptation JF - bioRxiv DO - 10.1101/2021.10.17.464699 SP - 2021.10.17.464699 AU - Nadia Herrera AU - Pascal D. Odermatt AU - Mark Voorhies AU - Rachel Nakagawa AU - Anita Sil AU - Fred Chang AU - Oren S. Rosenberg Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/17/2021.10.17.464699.abstract N2 - The ESX-1 system (6-kDa early secretory antigenic target (ESAT-6) secretion system-1) is essential for Mycobacterium tuberculosis pathogenesis and conjugal transfer in Mycobacterium smegmatis, yet little is known about how its function is regulated. Live-cell fluorescence microscopy showed natively expressed ESX-1 was organized into distinct foci predominantly observed at cell-cell contacts. These foci formed when two cells touched and required a fully assembled ESX-1 system in both bacteria, suggesting the generation of an ESX-1 megacomplex across multiple membranes. The emergence of ESX-1 foci and ESX-1 secretion was environmentally dependent: foci formed in low nitrogen environments in which secretion was suppressed, yet with increasing concentrations of nitrogen, ESX-1 systems diffused along the plasma membrane and secretion was activated. Genome-wide transcriptional profiling revealed ESX-1 dependent induction of genes required for the SOS response and error prone DNA replication in high nitrogen. Based on these findings, we propose a new model of ESX-1 function where ESX-1 localization and secretion are responsive to nitrogen levels and form an integral node in the mycobacterial response to neighboring cells and environmental adaptation.Competing Interest StatementThe authors have declared no competing interest. ER -