A glutathione-dependent detoxification system is required for formaldehyde resistance and optimal survival of Neisseria meningitidis in biofilms

Chen, Nathan H., Couñago, Rafael M., Djoko, Karrera Y., Jennings, Michael P., Apicella, Michael A., Kobe, Bostjan and McEwan, Alastair G. (2013) A glutathione-dependent detoxification system is required for formaldehyde resistance and optimal survival of Neisseria meningitidis in biofilms. Antioxidants and Redox Signaling, 18 7: 743-755. doi:10.1089/ars.2012.4749

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ282670_fulltext.pdf Full text (open access) application/pdf 957.44KB 62

Author Chen, Nathan H.
Couñago, Rafael M.
Djoko, Karrera Y.
Jennings, Michael P.
Apicella, Michael A.
Kobe, Bostjan
McEwan, Alastair G.
Title A glutathione-dependent detoxification system is required for formaldehyde resistance and optimal survival of Neisseria meningitidis in biofilms
Formatted title
A glutathione-dependent detoxification system is required for formaldehyde resistance and optimal survival of Neisseria meningitidis in biofilms
Journal name Antioxidants and Redox Signaling   Check publisher's open access policy
ISSN 1523-0864
1557-7716
Publication date 2013-03
Year available 2012
Sub-type Article (original research)
DOI 10.1089/ars.2012.4749
Open Access Status File (Author Post-print)
Volume 18
Issue 7
Start page 743
End page 755
Total pages 13
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Collection year 2013
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 20 November 2012. This is a copy of an article published in Antioxidants & Redox Signaling ©2013 copyright Mary Ann Liebert, Inc.; Antioxidants & Redox Signaling is available online at: http://online.liebertpub.com.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 02 Oct 2012, 15:37:23 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences