title: Depletion of CG-Specific Methylation in Mycoplasma hyorhinis Genomic DNA after Host Cell Invasion.
abstract: Adaptation to the environment requires pathogenic bacteria to alter their gene expression in order to increase long-term survival in the host. Here, we present the first experimental evidence that bacterial DNA methylation affects the intracellular survival of pathogenic Mycoplasma hyorhinis. Using bisulfite sequencing, we identified that the M. hyorhinis DNA methylation landscape was distinct in free-living M. hyorhinis relative to the internalized bacteria surviving in the infected human cells. We determined that genomic GATC sites were consistently highly methylated in the bacterial chromosome suggesting that the bacterial GATC-specific 5-methylcytosine DNA methyltransferase was fully functional both pre- and post-infection. In contrast, only the low CG methylation pattern was observed in the mycoplasma genome in the infective bacteria that invaded and then survived in the host cells. In turn, two distinct populations, with either high or low CG methylation, were detected in the M. hyorhinis cultures continually grown in the rich medium independently of host cells. We also identified that M. hyorhinis efficiently evaded endosomal degradation and uses exocytosis to exit infected human cells enabling re-infection of additional cells. The well-orchestrated changes in the chromosome methylation landscape play a major regulatory role in the mycoplasma life cycle.
authors.affiliation: Infectious & Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Chernov
authors.affiliation: Department of Infectious Disease & Pathology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Leticia
authors.initials: L
authors.lastname: Reyes
authors.affiliation: Infectious & Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Scott
authors.initials: S
authors.lastname: Peterson
authors.affiliation: Infectious & Inflammatory Disease Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America.
authors.forename: Alex Y
authors.initials: AY
authors.lastname: Strongin
mesh_terms: D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D015257:DNA-Cytosine Methylases / Q000378:metabolism; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D045790:Mycoplasma hyorhinis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D014327:Trophoblasts / Q000382:microbiology
chemical_list: D004269:DNA, Bacterial; C081573:DNA modification methylase SssI; D015257:DNA-Cytosine Methylases