title: Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate.
abstract: Lipooligosaccharide (LOS) is a major surface component of Moraxella catarrhalis and a possible virulence factor in the pathogenesis of human infections caused by this organism. The presence of LOS on the bacterium is an obstacle to the development of vaccines derived from whole cells or outer membrane components of the bacterium. An lpxA gene encoding UDP-N-acetylglucosamine acyltransferase responsible for the first step of lipid A biosynthesis was identified by the construction and characterization of an isogenic M. catarrhalis lpxA mutant in strain O35E. The resulting mutant was viable despite the complete loss of LOS. The mutant strain showed significantly decreased toxicity by the Limulus amebocyte lysate assay, reduced resistance to normal human serum, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. Importantly, the mutant elicited high levels of antibodies with bactericidal activity and provided protection against a challenge with the wild-type strain. These data suggest that the null LOS mutant is attenuated and may be a potential vaccine candidate against M. catarrhalis.
authors.affiliation: Vaccine Research Section, National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850, USA.
authors.forename: Daxin
authors.initials: D
authors.lastname: Peng
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Hong
authors.forename: Biswa P
authors.initials: BP
authors.lastname: Choudhury
authors.forename: Russell W
authors.initials: RW
authors.lastname: Carlson
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; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology*; D005798:Genes, Bacterial / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000201:enzymology / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D045828:Moraxellaceae Infections / Q000276:immunology* / Q000517:prevention & control; D009154:Mutation / Q000235:genetics; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology; D037521:Virulence Factors / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D014613:Vaccines, Attenuated; D037521:Virulence Factors; C023023:lipid-linked oligosaccharides; D000217:Acyltransferases; C050304:acyl-(acyl-carrier-protein)-UDP-N-acetylglucosamine acyltransferase