title: Complete Circular Genome Sequence of Successful ST8/SCCmecIV Community-Associated Methicillin-Resistant Staphylococcus aureus (OC8) in Russia: One-Megabase Genomic Inversion, IS256's Spread, and Evolution of Russia ST8-IV.
abstract: ST8/SCCmecIV community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has been a common threat, with large USA300 epidemics in the United States. The global geographical structure of ST8/SCCmecIV has not yet been fully elucidated. We herein determined the complete circular genome sequence of ST8/SCCmecIVc strain OC8 from Siberian Russia. We found that 36.0% of the genome was inverted relative to USA300. Two IS256, oppositely oriented, at IS256-enriched hot spots were implicated with the one-megabase genomic inversion (MbIN) and vSaβ split. The behavior of IS256 was flexible: its insertion site (att) sequences on the genome and junction sequences of extrachromosomal circular DNA were all divergent, albeit with fixed sizes. A similar multi-IS256 system was detected, even in prevalent ST239 healthcare-associated MRSA in Russia, suggesting IS256's strong transmission potential and advantage in evolution. Regarding epidemiology, all ST8/SCCmecIVc strains from European, Siberian, and Far Eastern Russia, examined had MbIN, and geographical expansion accompanied divergent spa types and resistance to fluoroquinolones, chloramphenicol, and often rifampicin. Russia ST8/SCCmecIVc has been associated with life-threatening infections such as pneumonia and sepsis in both community and hospital settings. Regarding virulence, the OC8 genome carried a series of toxin and immune evasion genes, a truncated giant surface protein gene, and IS256 insertion adjacent to a pan-regulatory gene. These results suggest that unique single ST8/spa1(t008)/SCCmecIVc CA-MRSA (clade, Russia ST8-IVc) emerged in Russia, and this was followed by large geographical expansion, with MbIN as an epidemiological marker, and fluoroquinolone resistance, multiple virulence factors, and possibly a multi-IS256 system as selective advantages.
authors.affiliation: Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.|Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tsai-Wen
authors.initials: TW
authors.lastname: Wan
authors.affiliation: Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.|Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.|Department of Microbiology, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Khokhlova
authors.affiliation: Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.|Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Iwao
authors.affiliation: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Higuchi
authors.affiliation: Department of Microbiology and Immunology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Hung
authors.affiliation: Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.|Department of Clinical and Fundamental Medicine, Far Eastern Federal University School of Biomedicine, Vladivostok, Russia.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Reva
authors.affiliation: Department of Venereal and Skin Diseases and Cosmetology, Pacific State Medical University, Vladivostok, Russia.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Singur
authors.affiliation: Department of Medical Microbiology and Molecular Epidemiology, Scientific Research Institute of Children's Infections, St. Petersburg, Russia.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Gostev
authors.affiliation: Department of Medical Microbiology and Molecular Epidemiology, Scientific Research Institute of Children's Infections, St. Petersburg, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Sidorenko
authors.affiliation: Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.|Department of Microbiology, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Peryanova
authors.affiliation: Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Alla B
authors.initials: AB
authors.lastname: Salmina
authors.affiliation: Department of Clinical and Fundamental Medicine, Far Eastern Federal University School of Biomedicine, Vladivostok, Russia.
authors.forename: Galina V
authors.initials: GV
authors.lastname: Reva
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Lee-Jene
authors.initials: LJ
authors.lastname: Teng
authors.affiliation: Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.|Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.|Department of Clinical and Fundamental Medicine, Far Eastern Federal University School of Biomedicine, Vladivostok, Russia.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D005075:Biological Evolution; D017714:Community-Acquired Infections / Q000382:microbiology* / Q000473:pathology; D004269:DNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D004270:DNA, Circular / Q000737:chemistry / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D004917:Erythromycin / Q000494:pharmacology; D016680:Genome, Bacterial; D005838:Genotype; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D012426:Russia; D017422:Sequence Analysis, DNA; D057345:Sequence Inversion; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004270:DNA, Circular; D012333:RNA, Messenger; D012336:RNA, Ribosomal, 16S; D004917:Erythromycin