TY - JOUR
T1 - Phasevarion mediated epigenetic gene regulation in Helicobacter pylori
AU - Srikhanta, Yogitha N
AU - Gorrell, Rebecca J
AU - Steen, Jason A
AU - Gawthorne, Jayde A
AU - Kwok, Terry
AU - Grimmond, Sean M
AU - Robins-Browne, Roy M
AU - Jennings, Michael P
PY - 2011
Y1 - 2011
N2 - Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a a??phasevariona??), via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16 of isolates). Microarray analysis comparing the wild-type P12modH5 ON strain to a P12I?modH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.
AB - Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes) that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression). In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M) system, controls expression of a phase-variable regulon of genes (a a??phasevariona??), via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16 of isolates). Microarray analysis comparing the wild-type P12modH5 ON strain to a P12I?modH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.
UR - http://www.ncbi.nlm.nih.gov/pubmed/22162751
U2 - 10.1371/journal.pone.0027569
DO - 10.1371/journal.pone.0027569
M3 - Article
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e27569
ER -