An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division

Abstract Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell division. We demonstrated that deletio...

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Autores principales:	Sibusiso Senzani, Dong Li, Ashima Bhaskar, Christopher Ealand, James Chang, Binayak Rimal, Chengyin Liu, Sung Joon Kim, Neeraj Dhar, Bavesh Kana
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/031e018e709b4bf4bfe02c6bebde8464
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spelling	oai:doaj.org-article:031e018e709b4bf4bfe02c6bebde84642021-12-02T11:40:52ZAn Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division10.1038/s41598-017-01184-72045-2322https://doaj.org/article/031e018e709b4bf4bfe02c6bebde84642017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01184-7https://doaj.org/toc/2045-2322Abstract Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell division. We demonstrated that deletion of MSMEG_6281 (Ami1) in Mycobacterium smegmatis resulted in the formation of cellular chains, illustrative of cells that were unable to complete division. Suprisingly, viability in the Δami1 mutant was maintained through atypical lateral branching, the products of which proceeded to form viable daughter cells. We showed that these lateral buds resulted from mislocalization of DivIVA, a major determinant in facilitating polar elongation in mycobacterial cells. Failure of Δami1 mutant cells to separate also led to dysregulation of FtsZ ring bundling. Loss of Ami1 resulted in defects in septal peptidoglycan turnover with release of excess cell wall material from the septum or newly born cell poles. We noted signficant accumulation of 3-3 crosslinked muropeptides in the Δami1 mutant. We further demonstrated that deletion of ami1 leads to increased cell wall permeability and enhanced susceptiblity to cell wall targeting antibiotics. Collectively, these data provide novel insight on cell division in actinobacteria and highlights a new class of potential drug targets for mycobacterial diseases.Sibusiso SenzaniDong LiAshima BhaskarChristopher EalandJames ChangBinayak RimalChengyin LiuSung Joon KimNeeraj DharBavesh KanaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sibusiso Senzani Dong Li Ashima Bhaskar Christopher Ealand James Chang Binayak Rimal Chengyin Liu Sung Joon Kim Neeraj Dhar Bavesh Kana An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
description	Abstract Mycobacteria possess a multi-layered cell wall that requires extensive remodelling during cell division. We investigated the role of an amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase, a peptidoglycan remodelling enzyme implicated in cell division. We demonstrated that deletion of MSMEG_6281 (Ami1) in Mycobacterium smegmatis resulted in the formation of cellular chains, illustrative of cells that were unable to complete division. Suprisingly, viability in the Δami1 mutant was maintained through atypical lateral branching, the products of which proceeded to form viable daughter cells. We showed that these lateral buds resulted from mislocalization of DivIVA, a major determinant in facilitating polar elongation in mycobacterial cells. Failure of Δami1 mutant cells to separate also led to dysregulation of FtsZ ring bundling. Loss of Ami1 resulted in defects in septal peptidoglycan turnover with release of excess cell wall material from the septum or newly born cell poles. We noted signficant accumulation of 3-3 crosslinked muropeptides in the Δami1 mutant. We further demonstrated that deletion of ami1 leads to increased cell wall permeability and enhanced susceptiblity to cell wall targeting antibiotics. Collectively, these data provide novel insight on cell division in actinobacteria and highlights a new class of potential drug targets for mycobacterial diseases.
format	article
author	Sibusiso Senzani Dong Li Ashima Bhaskar Christopher Ealand James Chang Binayak Rimal Chengyin Liu Sung Joon Kim Neeraj Dhar Bavesh Kana
author_facet	Sibusiso Senzani Dong Li Ashima Bhaskar Christopher Ealand James Chang Binayak Rimal Chengyin Liu Sung Joon Kim Neeraj Dhar Bavesh Kana
author_sort	Sibusiso Senzani
title	An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
title_short	An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
title_full	An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
title_fullStr	An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
title_full_unstemmed	An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division
title_sort	amidase_3 domain-containing n-acetylmuramyl-l-alanine amidase is required for mycobacterial cell division
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/031e018e709b4bf4bfe02c6bebde8464
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An Amidase_3 domain-containing N-acetylmuramyl-L-alanine amidase is required for mycobacterial cell division

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