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A thorough understanding of how <jats:italic>M. catarrhalis<\/jats:italic> can establish an infection and respond to different stressors encountered in the host is crucial for new drug-target identification. Formaldehyde is a highly cytotoxic compound that can be produced endogenously as a by-product of metabolism and exogenously from environmental sources. Pathways responsible for formaldehyde detoxification are thus essential and are found in all domains of life. The current work investigated the role of the system consisting of the <jats:italic>S<\/jats:italic>-hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase<jats:italic>,<\/jats:italic> and the <jats:italic>S<\/jats:italic>-formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process in <jats:italic>M. catarrhalis<\/jats:italic>. Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those of <jats:italic>Streptococcus pneumoniae<\/jats:italic>, which share the same biological niche. Isogenic mutants were constructed to study the function of the system in <jats:italic>M. catarrhalis<\/jats:italic>. A single <jats:italic>fghA<\/jats:italic> knockout mutant did not confer sensitivity to formaldehyde, while the <jats:italic>adhC\u2013fghA<\/jats:italic> double mutant is formaldehyde-sensitive. In addition, both mutants were significantly cleared in a murine pulmonary model of infection as compared to the wild type, demonstrating the system\u2019s importance for this pathogen\u2019s virulence. The respective phenotypes were reversed upon the genetic complementation of the mutants. To date, this is the first study investigating the role of the AdhC\u2013FghA system in formaldehyde detoxification and pathogenesis of <jats:italic>M. catarrhalis<\/jats:italic>.<\/jats:p>","DOI":"10.1007\/s00430-024-00785-0","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T20:01:38Z","timestamp":1709755298000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Moraxella catarrhalis AdhC\u2013FghA system is important for formaldehyde detoxification and protection against pulmonary clearance"],"prefix":"10.1007","volume":"213","author":[{"given":"Dina","family":"Othman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha M.","family":"Elhosseiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa N.","family":"Eltayeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed S.","family":"Attia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"issue":"9","key":"785_CR1","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/JCM.01146-16","volume":"54","author":"S Sillanp\u00e4\u00e4","year":"2016","unstructured":"Sillanp\u00e4\u00e4 S et al (2016) Moraxella catarrhalis might be more common than expected in acute otitis media in young Finnish children. 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