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Article

Functional Characterization of the N-Acetylmuramyl-l-Alanine Amidase, Ami1, from Mycobacterium abscessus

1
Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, CNRS UMR 9004, CEDEX 5, 34293 Montpellier, France
2
Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, Denmark
3
CEMIPAI CNRS UM UMS3725, CEDEX 5, 34293 Montpellier, France
4
Department of Chemistry, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark
5
Chemical Library Institut Curie/CNRS, CNRS UMR9187, INSERM U1196 and CNRS UMR3666, INSERM U1193, Université Paris-Saclay, F-91405 Orsay, France
6
INSERM, IRIM, 34293 Montpellier, France
*
Authors to whom correspondence should be addressed.
Present address: Institut für Mikrobiologie und Biochemie, Hochschule Geisenheim University, 65366 Geisenheim, Germany.
Present address: Centre for Inflammation, Faculty of Science, Centenary Institute and University of Technology Sydney, Sydney, NSW 2006, Australia.
Cells 2020, 9(11), 2410; https://doi.org/10.3390/cells9112410
Received: 6 October 2020 / Revised: 27 October 2020 / Accepted: 29 October 2020 / Published: 4 November 2020
Peptidoglycan (PG) is made of a polymer of disaccharides organized as a three-dimensional mesh-like network connected together by peptidic cross-links. PG is a dynamic structure that is essential for resistance to environmental stressors. Remodeling of PG occurs throughout the bacterial life cycle, particularly during bacterial division and separation into daughter cells. Numerous autolysins with various substrate specificities participate in PG remodeling. Expression of these enzymes must be tightly regulated, as an excess of hydrolytic activity can be detrimental for the bacteria. In non-tuberculous mycobacteria such as Mycobacterium abscessus, the function of PG-modifying enzymes has been poorly investigated. In this study, we characterized the function of the PG amidase, Ami1 from M. abscessus. An ami1 deletion mutant was generated and the phenotypes of the mutant were evaluated with respect to susceptibility to antibiotics and virulence in human macrophages and zebrafish. The capacity of purified Ami1 to hydrolyze muramyl-dipeptide was demonstrated in vitro. In addition, the screening of a 9200 compounds library led to the selection of three compounds inhibiting Ami1 in vitro. We also report the structural characterization of Ami1 which, combined with in silico docking studies, allows us to propose a mode of action for these inhibitors. View Full-Text
Keywords: N-acetylmuramyl-l-alanine amidase; peptidoglycan; drug screening; x-ray crystallography; Mycobacterium abscessus N-acetylmuramyl-l-alanine amidase; peptidoglycan; drug screening; x-ray crystallography; Mycobacterium abscessus
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MDPI and ACS Style

Küssau, T.; Van Wyk, N.; Johansen, M.D.; Alsarraf, H.M.A.B.; Neyret, A.; Hamela, C.; Sørensen, K.K.; Thygesen, M.B.; Beauvineau, C.; Kremer, L.; Blaise, M. Functional Characterization of the N-Acetylmuramyl-l-Alanine Amidase, Ami1, from Mycobacterium abscessus. Cells 2020, 9, 2410. https://doi.org/10.3390/cells9112410

AMA Style

Küssau T, Van Wyk N, Johansen MD, Alsarraf HMAB, Neyret A, Hamela C, Sørensen KK, Thygesen MB, Beauvineau C, Kremer L, Blaise M. Functional Characterization of the N-Acetylmuramyl-l-Alanine Amidase, Ami1, from Mycobacterium abscessus. Cells. 2020; 9(11):2410. https://doi.org/10.3390/cells9112410

Chicago/Turabian Style

Küssau, Tanja, Niël Van Wyk, Matt D. Johansen, Husam M.A.B. Alsarraf, Aymeric Neyret, Claire Hamela, Kasper K. Sørensen, Mikkel B. Thygesen, Claire Beauvineau, Laurent Kremer, and Mickaël Blaise. 2020. "Functional Characterization of the N-Acetylmuramyl-l-Alanine Amidase, Ami1, from Mycobacterium abscessus" Cells 9, no. 11: 2410. https://doi.org/10.3390/cells9112410

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