Project description:The complement system is an important part of the innate defense against invading pathogens. The ability to resist complement-mediated killing is considered to be an important virulence trait for the human-restricted respiratory tract pathogen M. catarrhalis, as most disease-associated M. catarrhalis isolates are complement-resistant. Here we studied the molecular basis of M. catarrhalis complement-resistance by transcriptome profiling upon exposure to 10% normal human serum (NHS).
Project description:Moraxella catarrhalis contains an N6-adenine DNA-methyltransferase (ModM3), that is subject to phase variable expression (random ON/OFF switching). Phase-variable switching of DNA methyltransferase activity results in the presence or absence of methylation at a specific target sequence, leading to co-ordinated, epigenetically-regulated switching of expression of multiple genes across the genome. The suite of genes thus regulated are known as a phasevarion (phase-variable regulon). Phase variation of modM is mediated at the translational level by a 5′-(CAAC)n-3′ tetranucleotide repeat tract present within its open reading frame (ORF). Analysis of the genomes of 51 M. catarrhalis strains identified six modM alleles (modM1-6) that vary in their target recognition domains. The modM3 allele is also overrepresented in middle ear isolates of M. catarrhalis from children with OM. Here we characterise the genes regulated in the ModM3 phasevarion and show that phase variation of the M.catarrhalis CCRI-195ME ModM3 epigenetically regulates the expression of a phasevarion containing multiple genes that are potentially important in the progression of otitis media.
Project description:Comparison of the gene expression profile of Moraxella catarrhalis grown in the presence of 20% pooled human sputum in chemically-defined medium relative to Moraxella catarrhalis grown in chemically-defined medium alone.
