Role of different moieties from the lipooligosaccharide molecule in biological activities of the Moraxella catarrhalis outer membrane

• Published in: The FEBS journal Vol. 274; no. 20; pp. 5350 - 5359
• Main Authors: Peng, Daxin, Hu, Wei-Gang, Choudhury, Biswa P, Muszyński, Artur, Carlson, Russell W, Gu, Xin-Xing
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2007; Blackwell Publishing Ltd
• Subjects: Adult; Animals; Antibodies, Bacterial - immunology; Antibodies, Bacterial - pharmacology; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antigens, Bacterial - blood; Antigens, Bacterial - immunology; Antigens, Bacterial - pharmacology; Bacterial Adhesion - immunology; Biochemistry; Cell Adhesion - physiology; Cell Membrane Structures - metabolism; Female; Genotype & phenotype; HeLa Cells; Humans; Lipid A - chemistry; Lipid A - immunology; Lipid A - metabolism; Lipids; lipooligosaccharide; Lipopolysaccharides - chemistry; Lipopolysaccharides - immunology; Lipopolysaccharides - metabolism; Membranes; Mice; Mice, Inbred BALB C; moiety; Molecular Sequence Data; Molecular structure; Moraxella (Branhamella) catarrhalis - growth & development; Moraxella (Branhamella) catarrhalis - pathogenicity; Moraxella catarrhalis; Moraxellaceae Infections - immunology; Moraxellaceae Infections - metabolism; Moraxellaceae Infections - pathology; Mutagenesis; Mutation; Nasal Lavage Fluid - microbiology; Nasopharynx - microbiology; NMR; Nuclear magnetic resonance; outer membrane; role; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2007.06060.x

Lipooligosaccharide (LOS), a major component of the outer membrane of Moraxella catarrhalis, consists of two major moieties: a lipid A and a core oligosaccharide (OS). The core OS can be dissected into a linker and three OS chains. To gain an insight into the biological activities of the LOS molecules of M. catarrhalis, we used a random transposon mutagenesis approach with an LOS specific monoclonal antibody to construct a serotype A O35Elgt3 LOS mutant. MALDI-TOF-MS of de-O-acylated LOS from the mutant and glycosyl composition, linkage, and NMR analysis of its OS indicated that the LOS contained a truncated core OS and consisted of a Glc-Kdo₂ (linker)-lipid A structure. Phenotypic analysis revealed that the mutant was similar to the wild-type strain in its growth rate, toxicity and susceptibility to hydrophobic reagents. However, the mutant was sensitive to bactericidal activity of normal human serum and had a reduced adherence to human epithelial cells. These data, combined with our previous data obtained from mutants which contained only lipid A or lacked LOS, suggest that the complete OS chain moiety of the LOS is important for serum resistance and adherence to epithelial cells, whereas the linker moiety is critical for maintenance of the outer membrane integrity and stability to preserve normal cell growth. Both the lipid A and linker moieties contribute to the LOS toxicity.