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

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

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/cells9112410
Journal or Publication Title: Cells
Volume: 9
Number: 11
Page Range: p. 2410
Date: 2020
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.3390/cells9112410
ISSN: 2073-4409
Date Deposited: 05 Jan 2021 05:16
Abstract:

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.

Creators:
Creators
Email
Küssau, Tanja
UNSPECIFIED
Van Wyk, Niël
UNSPECIFIED
Johansen, Matt D.
UNSPECIFIED
Alsarraf, Husam M. A. B.
UNSPECIFIED
Neyret, Aymeric
UNSPECIFIED
Hamela, Claire
UNSPECIFIED
Sørensen, Kasper K.
UNSPECIFIED
Thygesen, Mikkel B.
UNSPECIFIED
Beauvineau, Claire
UNSPECIFIED
Kremer, Laurent
UNSPECIFIED
Blaise, Mickaël
UNSPECIFIED
Last Modified: 05 Jan 2021 05:16
URI: https://eprints.centenary.org.au/id/eprint/921

Actions (login required)

View Item View Item