The Moraxella catarrhalis AdhC –FghA system is important for formaldehyde detoxification and protection against pulmonary clearance

AbstractMultidrug-resistant clinical isolates ofMoraxella catarrhalis have emerged, increasing the demand for the identification of new treatment and prevention strategies. A thorough understanding of howM. catarrhalis 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 theS-hydroxymethyl alcohol dehydrogenase (AdhC), a Zn-dependent class III alcohol dehydrogenase, and theS-formyl glutathione hydrolase (FghA) in the formaldehyde detoxification process inM. catarrhalis. Bioinformatics showed that the components of the system are conserved across the species and are highly similar to those ofStreptococcus pneumoniae, which share the same biological niche. Isogenic mutants were constructed to study the function of the system inM. catarrhalis. A singlefghA knockout mutant did not confer sensitivity to formaldehyde, while theadhC –fghA 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 ’s importance for this pathogen’s virulence. The re...
Source: Medical Microbiology and Immunology - Category: Microbiology Source Type: research