Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis

Mycobacterium tuberculosis, the causative agent of tuberculosis remains a global health concern, further compounded by the high rates of HIV-TB co-infection and emergence of multi- and extensive drug resistant TB, all of which have hampered efforts to eradicate this disease. As a result, novel anti-...

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Autores principales:	Andrea Olga Papadopoulos, Christopher Ealand, Bhavna Gowan Gordhan, Michael VanNieuwenhze, Bavesh Davandra Kana
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c9e5c7f351ab43de95bc35056cd5715b
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spelling	oai:doaj.org-article:c9e5c7f351ab43de95bc35056cd5715b2021-11-25T06:13:56ZCharacterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis1932-6203https://doaj.org/article/c9e5c7f351ab43de95bc35056cd5715b2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594824/?tool=EBIhttps://doaj.org/toc/1932-6203Mycobacterium tuberculosis, the causative agent of tuberculosis remains a global health concern, further compounded by the high rates of HIV-TB co-infection and emergence of multi- and extensive drug resistant TB, all of which have hampered efforts to eradicate this disease. As a result, novel anti-tubercular interventions are urgently required, with the peptidoglycan component of the M. tuberculosis cell wall emerging as an attractive drug target. Peptidoglycan M23 endopeptidases can function as active cell wall hydrolases or degenerate activators of hydrolases in a variety of bacteria, contributing to important processes such as bacterial growth, division and virulence. Herein, we investigate the function of the Rv0950-encoded putative M23 endopeptidase in M. tuberculosis. In silico analysis revealed that this protein is conserved in mycobacteria, with a zinc-binding catalytic site predictive of hydrolytic activity. Transcript analysis indicated that expression of Rv0950c was elevated during lag and log phases of growth and reduced in stationary phase. Deletion of Rv0950c yielded no defects in growth, colony morphology, antibiotic susceptibility or intracellular survival but caused a reduction in cell length. Staining with a monopeptide-derived fluorescent D-amino acid, which spatially reports on sites of active PG biosynthesis or repair, revealed an overall reduction in uptake of the probe in ΔRv0950c. When stained with a dipeptide probe in the presence of cell wall damaging agents, the ΔRv0950c mutant displayed reduced sidewall labelling. As bacterial peptidoglycan metabolism is important for survival and pathogenesis, the role of Rv0950c and other putative M23 endopeptidases in M. tuberculosis should be explored further.Andrea Olga PapadopoulosChristopher EalandBhavna Gowan GordhanMichael VanNieuwenhzeBavesh Davandra KanaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea Olga Papadopoulos Christopher Ealand Bhavna Gowan Gordhan Michael VanNieuwenhze Bavesh Davandra Kana Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
description	Mycobacterium tuberculosis, the causative agent of tuberculosis remains a global health concern, further compounded by the high rates of HIV-TB co-infection and emergence of multi- and extensive drug resistant TB, all of which have hampered efforts to eradicate this disease. As a result, novel anti-tubercular interventions are urgently required, with the peptidoglycan component of the M. tuberculosis cell wall emerging as an attractive drug target. Peptidoglycan M23 endopeptidases can function as active cell wall hydrolases or degenerate activators of hydrolases in a variety of bacteria, contributing to important processes such as bacterial growth, division and virulence. Herein, we investigate the function of the Rv0950-encoded putative M23 endopeptidase in M. tuberculosis. In silico analysis revealed that this protein is conserved in mycobacteria, with a zinc-binding catalytic site predictive of hydrolytic activity. Transcript analysis indicated that expression of Rv0950c was elevated during lag and log phases of growth and reduced in stationary phase. Deletion of Rv0950c yielded no defects in growth, colony morphology, antibiotic susceptibility or intracellular survival but caused a reduction in cell length. Staining with a monopeptide-derived fluorescent D-amino acid, which spatially reports on sites of active PG biosynthesis or repair, revealed an overall reduction in uptake of the probe in ΔRv0950c. When stained with a dipeptide probe in the presence of cell wall damaging agents, the ΔRv0950c mutant displayed reduced sidewall labelling. As bacterial peptidoglycan metabolism is important for survival and pathogenesis, the role of Rv0950c and other putative M23 endopeptidases in M. tuberculosis should be explored further.
format	article
author	Andrea Olga Papadopoulos Christopher Ealand Bhavna Gowan Gordhan Michael VanNieuwenhze Bavesh Davandra Kana
author_facet	Andrea Olga Papadopoulos Christopher Ealand Bhavna Gowan Gordhan Michael VanNieuwenhze Bavesh Davandra Kana
author_sort	Andrea Olga Papadopoulos
title	Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
title_short	Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
title_full	Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
title_fullStr	Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
title_full_unstemmed	Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis
title_sort	characterisation of a putative m23-domain containing protein in mycobacterium tuberculosis
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/c9e5c7f351ab43de95bc35056cd5715b
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Characterisation of a putative M23-domain containing protein in Mycobacterium tuberculosis

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