Stress-Induced Reorganization of the Mycobacterial Membrane Domain

ABSTRACT Cell elongation occurs primarily at the mycobacterial cell poles, but the molecular mechanisms governing this spatial regulation remain elusive. We recently reported the presence of an intracellular membrane domain (IMD) that was spatially segregated from the conventional plasma membrane in...

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Autores principales:	Jennifer M. Hayashi, Kirill Richardson, Emily S. Melzer, Steven J. Sandler, Bree B. Aldridge, M. Sloan Siegrist, Yasu S. Morita
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Mycobacterium cell envelope membrane proteins membranes peptidoglycan stress response Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/d4024532b5e649359bab4c5e0edff90c
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spelling	oai:doaj.org-article:d4024532b5e649359bab4c5e0edff90c2021-11-15T15:53:25ZStress-Induced Reorganization of the Mycobacterial Membrane Domain10.1128/mBio.01823-172150-7511https://doaj.org/article/d4024532b5e649359bab4c5e0edff90c2018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01823-17https://doaj.org/toc/2150-7511ABSTRACT Cell elongation occurs primarily at the mycobacterial cell poles, but the molecular mechanisms governing this spatial regulation remain elusive. We recently reported the presence of an intracellular membrane domain (IMD) that was spatially segregated from the conventional plasma membrane in Mycobacterium smegmatis. The IMD is enriched in the polar region of actively elongating cells and houses many essential enzymes involved in envelope biosynthesis, suggesting its role in spatially restricted elongation at the cell poles. Here, we examined reorganization of the IMD when the cells are no longer elongating. To monitor the IMD, we used a previously established reporter strain expressing fluorescent IMD markers and grew it to the stationary growth phase or exposed the cells to nutrient starvation. In both cases, the IMD was delocalized from the cell pole and distributed along the sidewall. Importantly, the IMD could still be isolated biochemically by density gradient fractionation, indicating its maintenance as a membrane domain. Chemical and genetic inhibition of peptidoglycan biosynthesis led to the delocalization of the IMD, suggesting the suppression of peptidoglycan biosynthesis as a trigger of spatial IMD rearrangement. Starved cells with a delocalized IMD can resume growth upon nutrient repletion, and polar enrichment of the IMD coincides with the initiation of cell elongation. These data reveal that the IMD is a membrane domain with the unprecedented capability of subcellular repositioning in response to the physiological conditions of the mycobacterial cell. IMPORTANCE Mycobacteria include medically important species, such as the human tuberculosis pathogen Mycobacterium tuberculosis. The highly impermeable cell envelope is a hallmark of these microbes, and its biosynthesis is a proven chemotherapeutic target. Despite the accumulating knowledge regarding the biosynthesis of individual envelope components, the regulatory mechanisms behind the coordinated synthesis of the complex cell envelope remain elusive. We previously reported the presence of a metabolically active membrane domain enriched in the elongating poles of actively growing mycobacteria. However, the spatiotemporal dynamics of the membrane domain in response to stress have not been examined. Here, we show that the membrane domain is spatially reorganized when growth is inhibited in the stationary growth phase, under nutrient starvation, or in response to perturbation of peptidoglycan biosynthesis. Our results suggest that mycobacteria have a mechanism to spatiotemporally coordinate the membrane domain in response to metabolic needs under different growth conditions.Jennifer M. HayashiKirill RichardsonEmily S. MelzerSteven J. SandlerBree B. AldridgeM. Sloan SiegristYasu S. MoritaAmerican Society for MicrobiologyarticleMycobacteriumcell envelopemembrane proteinsmembranespeptidoglycanstress responseMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium cell envelope membrane proteins membranes peptidoglycan stress response Microbiology QR1-502
spellingShingle	Mycobacterium cell envelope membrane proteins membranes peptidoglycan stress response Microbiology QR1-502 Jennifer M. Hayashi Kirill Richardson Emily S. Melzer Steven J. Sandler Bree B. Aldridge M. Sloan Siegrist Yasu S. Morita Stress-Induced Reorganization of the Mycobacterial Membrane Domain
description	ABSTRACT Cell elongation occurs primarily at the mycobacterial cell poles, but the molecular mechanisms governing this spatial regulation remain elusive. We recently reported the presence of an intracellular membrane domain (IMD) that was spatially segregated from the conventional plasma membrane in Mycobacterium smegmatis. The IMD is enriched in the polar region of actively elongating cells and houses many essential enzymes involved in envelope biosynthesis, suggesting its role in spatially restricted elongation at the cell poles. Here, we examined reorganization of the IMD when the cells are no longer elongating. To monitor the IMD, we used a previously established reporter strain expressing fluorescent IMD markers and grew it to the stationary growth phase or exposed the cells to nutrient starvation. In both cases, the IMD was delocalized from the cell pole and distributed along the sidewall. Importantly, the IMD could still be isolated biochemically by density gradient fractionation, indicating its maintenance as a membrane domain. Chemical and genetic inhibition of peptidoglycan biosynthesis led to the delocalization of the IMD, suggesting the suppression of peptidoglycan biosynthesis as a trigger of spatial IMD rearrangement. Starved cells with a delocalized IMD can resume growth upon nutrient repletion, and polar enrichment of the IMD coincides with the initiation of cell elongation. These data reveal that the IMD is a membrane domain with the unprecedented capability of subcellular repositioning in response to the physiological conditions of the mycobacterial cell. IMPORTANCE Mycobacteria include medically important species, such as the human tuberculosis pathogen Mycobacterium tuberculosis. The highly impermeable cell envelope is a hallmark of these microbes, and its biosynthesis is a proven chemotherapeutic target. Despite the accumulating knowledge regarding the biosynthesis of individual envelope components, the regulatory mechanisms behind the coordinated synthesis of the complex cell envelope remain elusive. We previously reported the presence of a metabolically active membrane domain enriched in the elongating poles of actively growing mycobacteria. However, the spatiotemporal dynamics of the membrane domain in response to stress have not been examined. Here, we show that the membrane domain is spatially reorganized when growth is inhibited in the stationary growth phase, under nutrient starvation, or in response to perturbation of peptidoglycan biosynthesis. Our results suggest that mycobacteria have a mechanism to spatiotemporally coordinate the membrane domain in response to metabolic needs under different growth conditions.
format	article
author	Jennifer M. Hayashi Kirill Richardson Emily S. Melzer Steven J. Sandler Bree B. Aldridge M. Sloan Siegrist Yasu S. Morita
author_facet	Jennifer M. Hayashi Kirill Richardson Emily S. Melzer Steven J. Sandler Bree B. Aldridge M. Sloan Siegrist Yasu S. Morita
author_sort	Jennifer M. Hayashi
title	Stress-Induced Reorganization of the Mycobacterial Membrane Domain
title_short	Stress-Induced Reorganization of the Mycobacterial Membrane Domain
title_full	Stress-Induced Reorganization of the Mycobacterial Membrane Domain
title_fullStr	Stress-Induced Reorganization of the Mycobacterial Membrane Domain
title_full_unstemmed	Stress-Induced Reorganization of the Mycobacterial Membrane Domain
title_sort	stress-induced reorganization of the mycobacterial membrane domain
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/d4024532b5e649359bab4c5e0edff90c
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Stress-Induced Reorganization of the Mycobacterial Membrane Domain

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