Project description:iTRAQ quantitative mass spec of proteins differentially regulated by biphasic switching of modA methyltransferase alleles in the human pathogen non-typeable Haemophilus influenzae
Project description:Characterization of a novel haem-binding protein produced by Haemophilus haemolyticus, isolated and purified from non-typeable Haemophilus influenzae (NTHi)-inhibitory substance.
Project description:Characterization of a novel haem-binding protein that is secreted by two Haemophilus haemolyticus isolates, BW1 and RHH122, and that inhibits the growth of the pathogen non-typeable Haemophilus influenzae (NTHi) in vitro.
Project description:Non-typeable Haemophilus influenzae (NTHi) contains an N6-adenine DNA-methyltransferase (ModA), that is subject to phase variable expression (random ON/OFF switching). Five modA alleles, modA2, 4, 5, 9 and 10, account for over two-thirds of clinical otitis media isolates surveyed. Single Molecule Real Time (SMRT) methylome analysis identified the DNA recognition motifs for all five of these modA alleles. Phase variation of these alleles regulated multiple proteins, including vaccine candidates. ON/OFF switching of modA alleles resulted in differential regulation of key virulence phenotypes, such as antibiotic resistance (modA2, 5, 10), biofilm formation (modA2) and immunoevasion (modA4). Analysis of the modA2 strain, 723, in the chinchilla model of otitis media showed a clear selection for switching from modA2OFF to ON in the middle ear. This is the first report of a biphasic epigenetic switch controlling bacterial virulence, immunoevasion and niche adaptation in an animal model system
