Guy, C.S., Cooper, C. orcid.org/0000-0003-4855-4187, Karlikowska, M. orcid.org/0000-0003-4996-0638 et al. (10 more authors) (2025) The deacetylase NagA mediates the remodelling and recycling of peptidoglycan derived amino sugars in mycobacteria. Journal of Biological Chemistry. 110597. ISSN: 0021-9258
Abstract
Many bacterial species are known to recover peptidoglycan (PG) fragments released from remodelling of their cell walls during growth and cell division. These PG fragments not only provide an essential energy resource, especially in nutrient restricted environments, but also play a critical role in influencing infection. Yet whether mycobacteria have the capacity to recycle their PG, or not, has still not been resolved. In this study we show that NagA, an N-acetylglucosamine-6-phosphate (GlcNAc-6-P) deacetylase, is essential for coordinating the remodelling and recycling of an amino sugar component released from the mycobacterial cell wall. We show that NagA is exclusively responsible for GlcNAc-6-P deacetylation and is pivotal for the de novo synthesis of core cell wall building blocks. Indeed, a nagA deletion mutant exhibited an altered composition of the cell envelope, smaller overall cell size, defective biofilm formation, and enhanced susceptibility to cell wall targeting agents. Moreover, uptake analysis and profiling of the amino-sugar pool revealed that NagA inactivation blocks N-acetylglucosamine (GlcNAc) import and has a pronounced effect on the fate and levels of the intracellular amino sugar pool. Loss of NagA led to the up- and down-regulation of proteins involved in cell wall biosynthesis, thereby altering cell wall homeostasis. Overall, our data highlights the importance of an overlooked yet conserved component in an important PG salvage pathway in mycobacteria, in which NagA provides a unique GlcNAc sensing mechanism, thus acting as a checkpoint for regulating the recovery and reuse of PG fragments.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | ® 2025 The authors. User License: Creative Commons Attribution (CC BY 4.0) | Elsevier's open access license policy - http://creativecommons.org/licenses/by/4.0/ |
Keywords: | Biochemistry and Cell Biology; Biological Sciences; Infectious Diseases; Factors relating to the physical environment; Biological and endogenous factors; Normal biological development and functioning; Infection; Generic health relevance |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > School of Chemical, Materials and Biological Engineering The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/L024209/1 BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/W013800/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Aug 2025 13:42 |
Last Modified: | 29 Aug 2025 13:42 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.jbc.2025.110597 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:230789 |