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A Glutathione-Dependent Detoxification System Is Required for Formaldehyde Resistance and Optimal Survival ofNeisseria meningitidisin Biofilms

Chen, Nathan H.; Couñago, Rafael M.; Djoko, Karrera Y.; Jennings, Michael P.; Apicella, Michael A.; Kobe, Bostjan; McEwan, Alastair G.

Authors

Nathan H. Chen

Rafael M. Couñago

Michael P. Jennings

Michael A. Apicella

Bostjan Kobe

Alastair G. McEwan



Abstract

Aim: The glutathione-dependent AdhC-EstD formaldehyde detoxification system is found in eukaryotes and prokaryotes. It is established that it confers protection against formaldehyde that is produced from environmental sources or methanol metabolism. Thus, its presence in the human host-adapted bacterial pathogen Neisseria meningitidis is intriguing. This work defined the biological function of this system in the meningococcus using phenotypic analyses of mutants linked to biochemical and structural characterization of purified enzymes. Results: We demonstrated that mutants in the adhC and/or estD were sensitive to killing by formaldehyde. Inactivation of adhC and/or estD also led to a loss of viability in biofilm communities, even in the absence of exogenous formaldehyde. Detailed biochemical and structural analyses of the esterase component demonstrated that S-formylglutathione was the only biologically relevant substrate for EstD. We further showed that an absolutely conserved cysteine residue was covalently modified by S-glutathionylation. This leads to inactivation of EstD. Innovation: The results provide several conceptual innovations. They provide a new insight into formaldehyde detoxification in bacteria that do not generate formaldehyde during the catabolism of methanol. Our results also indicate that the conserved cysteine, found in all EstD enzymes from humans to microbes, is a site of enzyme regulation, probably via S-glutathionylation. Conclusion: The adhc-estD system protects against formaldehyde produced during endogenous metabolism.

Citation

Chen, N. H., Couñago, R. M., Djoko, K. Y., Jennings, M. P., Apicella, M. A., Kobe, B., & McEwan, A. G. (2013). A Glutathione-Dependent Detoxification System Is Required for Formaldehyde Resistance and Optimal Survival ofNeisseria meningitidisin Biofilms. Antioxidants and Redox Signaling, 18(7), 743-755. https://doi.org/10.1089/ars.2012.4749

Journal Article Type Article
Acceptance Date Sep 2, 2012
Online Publication Date Nov 20, 2012
Publication Date 2013-01
Deposit Date Sep 6, 2017
Journal Antioxidants and Redox Signaling
Print ISSN 1523-0864
Electronic ISSN 1557-7716
Publisher Mary Ann Liebert
Peer Reviewed Peer Reviewed
Volume 18
Issue 7
Pages 743-755
DOI https://doi.org/10.1089/ars.2012.4749
Public URL https://durham-repository.worktribe.com/output/1350259