Mycobacterium smegmatis HtrA Blocks the Toxic Activity of a Putative Cell Wall Amidase.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
21 05 2019
Historique:
received: 02 05 2018
revised: 14 10 2018
accepted: 13 12 2018
entrez: 23 5 2019
pubmed: 23 5 2019
medline: 9 7 2020
Statut: ppublish

Résumé

Mycobacterium tuberculosis, the causative agent of tuberculosis, withstands diverse environmental stresses in the host. The periplasmic protease HtrA is required only to survive extreme conditions in most bacteria but is predicted to be essential for normal growth in mycobacteria. We confirm that HtrA is indeed essential in Mycobacterium smegmatis and interacts with another essential protein of unknown function, LppZ. However, the loss of any of three unlinked genes, including those encoding Ami3, a peptidoglycan muramidase, and Pmt, a mannosyltransferase, suppresses the essentiality of both HtrA and LppZ, indicating the functional relevance of these genes' protein products. Our data indicate that HtrA-LppZ is required to counteract the accumulation of active Ami3, which is toxic under the stabilizing influence of Pmt-based mannosylation. This suggests that HtrA-LppZ blocks the toxicity of a cell wall enzyme to maintain mycobacterial homeostasis.

Identifiants

pubmed: 31116989
pii: S2211-1247(18)32008-4
doi: 10.1016/j.celrep.2018.12.063
pmc: PMC6538288
mid: NIHMS1530009
pii:
doi:

Substances chimiques

Bacterial Proteins 0
Heat-Shock Proteins 0
Lipoproteins 0
Periplasmic Proteins 0
Mannosyltransferases EC 2.4.1.-
Muramidase EC 3.2.1.17
DegP protease EC 3.4.21.-
Serine Endopeptidases EC 3.4.21.-
EJL amidase EC 3.5.1.-
N-Acetylmuramoyl-L-alanine Amidase EC 3.5.1.28

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2468-2479.e3

Subventions

Organisme : NIAID NIH HHS
ID : F31 AI131502
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI107774
Pays : United States

Informations de copyright

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Katherine J Wu (KJ)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Cara C Boutte (CC)

Department of Biology, University of Texas at Arlington, Arlington, TX 76019, USA.

Thomas R Ioerger (TR)

Department of Computer Science, Texas A&M University, College Station, TX 77843, USA.

Eric J Rubin (EJ)

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: erubin@hsph.harvard.edu.

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