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Protein scaffold involving MSMEG_1285 maintains cell wall organization and mediates penicillin sensitivity in mycobacteria
Author(s) -
VeyronChurlet Romain,
Saliou JeanMichel,
Locht Camille
Publication year - 2020
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15232
Subject(s) - peptidoglycan , mycobacterium smegmatis , penicillin binding proteins , cell wall , lipid ii , bacterial cell structure , penicillin , biochemistry , biosynthesis , microbiology and biotechnology , biology , antibiotics , enzyme , bacteria , mycobacterium tuberculosis , genetics , medicine , tuberculosis , pathology
Protein–protein interactions are key in mycobacterial physiology, notably during the biosynthesis of the very peculiar mycobacterial cell wall. In this paper, we demonstrate that MSMEG_1285 interacts with PonA1, a bifunctional penicillin‐binding protein involved in peptidoglycan biosynthesis. Deletion of MSMEG_1285 enhances Mycobacterium smegmatis resistance to penicillin antibiotics, a phenotype that is exacerbated by the additional deletion of hbhA . This also led to a substantial decrease in the amounts of porins in the cell wall, which are necessary for the import of small and hydrophilic β‐lactams. Deletion of both MSMEG_1285 and hbhA provoked an over‐representation of several enzymes involved in peptidoglycan degradation. Thus, we propose that MSMEG_1285 is part of a protein scaffold, which also involves PonA1 and HbhA, and that it is responsible for the tight regulation of peptidoglycan hydrolysis. This study provides a better understanding of the mycobacterial physiology, which is an essential step for strengthening the action of drugs that specifically target peptidoglycan biosynthesis.