title: Mapping epigenetic changes to the host cell genome induced by Burkholderia pseudomallei reveals pathogen-specific and pathogen-generic signatures of infection.
abstract: The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling. A comparison of our data with reported methylome changes in cells infected with M. tuberculosis revealed commonality of differentially methylated genes, including genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK), actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1), and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that pathogenic-specific and pathogen-common changes in the methylome occur following infection.
authors.affiliation: College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Deniz
authors.initials: D
authors.lastname: Cizmeci
authors.affiliation: University of Exeter Medical School, Exeter University, Exeter, United Kingdom.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Dempster
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Olivia L
authors.initials: OL
authors.lastname: Champion
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Sariqa
authors.initials: S
authors.lastname: Wagley
authors.affiliation: College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Ozgur E
authors.initials: OE
authors.lastname: Akman
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Joann L
authors.initials: JL
authors.lastname: Prior
authors.affiliation: School of Life Sciences, University of Warwick, United Kingdom.
authors.forename: Orkun S
authors.initials: OS
authors.lastname: Soyer
authors.affiliation: University of Exeter Medical School, Exeter University, Exeter, United Kingdom.|Institute of Psychiatry, Psychology &Neuroscience, King's College London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.affiliation: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D019121:Burkholderia Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015894:Genome, Human; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007938:Leukemia / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D014407:Tumor Cells, Cultured