Virulence genes in Moraxella catarrhalis lipopolysaocharide biosynthesis pathway

摘要

We have previously found several potential virulence genes involved in Moraxella catarrhalis lipooligosaccharide (LOS) biosynthesis pathway. The genes include kdtA, lgt3, lpxA and lpxL/X. Using either a random transposon mutagenesis or bioinformatics approach, each corresponding knockout mutant has been generated and its truncated LOS structure confirmed by MALDI-TOF MS, glycosyl composition, linkage, and NMR analyses of de-O-acylated LOS or oligosaccharide (OS) from the mutant. Phe-notypic studies revealed that the mutants showed different patterns in their growth rate, toxicity and susceptibility to hydrophobic reagents. However, most mutants with truncated LOS structure in OS and/or lipid A presented reduced resistance to the bactericidal activity of normal human serum, reduced adherence to human epithelial cells, and increased bacterial clearance in animals. Our data suggest that a complete OS moiety of the LOS is important for serum resistance and adherence to epithelial cells, and both the OS and lipid A moieties contribute to the LOS virulence.