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bioRxiv · 10.1101/2021.10.17.464699

The ESX-1 secretion system senses bacterial contact and prepares mycobacteria for environmental adaptation

Herrera, N.·Odermatt, P. D.·Voorhies, M.·Nakagawa, R.·Sil, A.·Chang, F.·Rosenberg, O. S.
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Abstract

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.

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Herrera, N., Odermatt, P. D., Voorhies, M., Nakagawa, R., Sil, A., Chang, F., Rosenberg, O. S.. 2021-10-17. The ESX-1 secretion system senses bacterial contact and prepares mycobacteria for environmental adaptation. https://doi.org/10.1101/2021.10.17.464699

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