4b6g

Publication Abstract from PubMed

<b>Aim:</b> 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 <i>Neisseria meningitidis</i> is intriguing. This work defined the biological function of this system in the meningococcus using phenotypic analyses of mutants linked to biochemical and structural characterisation of purified enzymes. <b>Results:</b> We demonstrated that mutants in the <i>adhC</i> and/or <i>estD</i> were sensitive to killing by formaldehyde. Inactivation of <i>adhC</i> and/or <i>estD</i> 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 <i>S</i>-formylglutathione was the only biologically relevant substrate for EstD. We further showed that an absolutely conserved cysteine residue was covalently modified by <i>S</i>-glutathionylation. This leads to inactivation of EstD. <b>Innovation:</b> The results provide several conceptual innovations. They provide 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 <i>S</i>-glutathionylation. <b>Conclusion:</b> The <i>adhC/estD</i> system protects against formaldehyde produced during endogenous metabolism.

A glutathione-dependent detoxification system is required for formaldehyde resistance and optimal survival of <i>Neisseria meningitidis</i> in biofilms.,Chen NH, Counago RM, Djoko KY, Jennings MP, Apicella MA, Kobe B, McEwan AG Antioxid Redox Signal. 2012 Sep 3. PMID:22937752^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.