title: Late acyltransferase genes lpxX and lpxL jointly contribute to the biological activities of Moraxella catarrhalis.
abstract: Lipo-oligosaccharide (LOS) is a major surface component and virulence factor of the human respiratory pathogen Moraxella catarrhalis. Two late acyltransferase genes, lpxX and lpxL, have been identified involved in the incorporation of acyloxyacyl-linked secondary acyl chains into lipid A during M. catarrhalis LOS biosynthesis. In this study, a double mutant with a deletion of both the lpxX and lpxL genes in M. catarrhalis strain O35E was constructed and named O35ElpxXL. Structural analysis of lipid A showed that the O35ElpxXL mutant lacked two decanoic acids (10 : 0) and one dodecanoic (lauric) acid (12 : 0). In comparison with the O35E parental strain and the single mutants O35ElpxX and O35ElpxL, the double mutant O35ElpxXL displayed prominently decreased endotoxin content, reduced resistance to normal human serum and accelerated bacterial clearance at 0, 3 and 6 h after an aerosol challenge in a mouse model of bacterial pulmonary clearance. These results indicate that these two genes encoding late acyltransferases responsible for lipid A biosynthesis jointly contribute to the biological activities and pathogenicity of M. catarrhalis. The double mutant O35ElpxXL with dramatically reduced toxicity is proposed as a potential vaccine candidate against M. catarrhalis infections for further investigation.
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Dabin
authors.initials: D
authors.lastname: Ren
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Daxin
authors.initials: D
authors.lastname: Peng
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Artur
authors.initials: A
authors.lastname: Muszyński
authors.affiliation: Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Carlson
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
authors.forename: Xin-Xing
authors.initials: XX
authors.lastname: Gu
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001770:Blood Bactericidal Activity; D005260:Female; D006801:Humans; D008050:Lipid A / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D001936:Moraxella catarrhalis / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D045828:Moraxellaceae Infections / Q000276:immunology / Q000382:microbiology*; D009154:Mutation; D014774:Virulence; D037521:Virulence Factors
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D008050:Lipid A; D008070:Lipopolysaccharides; D037521:Virulence Factors; D000217:Acyltransferases; C118473:LpxL protein, bacteria