title: Healthcare- and Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) and Fatal Pneumonia with Pediatric Deaths in Krasnoyarsk, Siberian Russia: Unique MRSA's Multiple Virulence Factors, Genome, and Stepwise Evolution.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a common multidrug-resistant (MDR) pathogen. We herein discussed MRSA and its infections in Krasnoyarsk, Siberian Russia between 2007 and 2011. The incidence of MRSA in 3,662 subjects was 22.0% and 2.9% for healthcare- and community-associated MRSA (HA- and CA-MRSA), respectively. The 15-day mortality rates for MRSA hospital- and community-acquired pneumonia (HAP and CAP) were 6.5% and 50%, respectively. MRSA CAP cases included pediatric deaths; of the MRSA pneumonia episodes available, ≥27.3% were associated with bacteremia. Most cases of HA-MRSA examined exhibited ST239/spa3(t037)/SCCmecIII.1.1.2 (designated as ST239Kras), while all CA-MRSA cases examined were ST8/spa1(t008)/SCCmecIV.3.1.1(IVc) (designated as ST8Kras). ST239Kras and ST8Kras strongly expressed cytolytic peptide (phenol-soluble modulin α, PSMα; and δ-hemolysin, Hld) genes, similar to CA-MRSA. ST239Kras pneumonia may have been attributed to a unique set of multiple virulence factors (MVFs): toxic shock syndrome toxin-1 (TSST-1), elevated PSMα/Hld expression, α-hemolysin, the staphylococcal enterotoxin SEK/SEQ, the immune evasion factor SCIN/SAK, and collagen adhesin. Regarding ST8Kras, SEA was included in MVFs, some of which were common to ST239Kras. The ST239Kras (strain OC3) genome contained: a completely unique phage, φSa7-like (W), with no att repetition; S. aureus pathogenicity island SaPI2R, the first TSST-1 gene-positive (tst+) SaPI in the ST239 lineage; and a super copy of IS256 (≥22 copies/genome). ST239Kras carried the Brazilian SCCmecIII.1.1.2 and United Kingdom-type tst. ST239Kras and ST8Kras were MDR, with the same levofloxacin resistance mutations; small, but transmissible chloramphenicol resistance plasmids spread widely enough to not be ignored. These results suggest that novel MDR and MVF+ HA- and CA-MRSA (ST239Kras and ST8Kras) emerged in Siberian Russia (Krasnoyarsk) associated with fatal pneumonia, and also with ST239Kras, a new (Siberian Russian) clade of the ST239 lineage, which was created through stepwise evolution during its potential transmission route of Brazil-Europe-Russia/Krasnoyarsk, thereby selective advantages from unique MVFs and the MDR.
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; Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.
authors.forename: Olga E
authors.initials: OE
authors.lastname: Khokhlova
authors.affiliation: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; 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; 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 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: Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia; Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.
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: Tomomi
authors.initials: T
authors.lastname: Takano
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: Krasnoyarsk Regional Center for Prevention and Control of AIDS and Infectious Diseases, Krasnoyarsk, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Yachenko
authors.affiliation: City Clinical Hospital No. 7, Krasnoyarsk, Russia; Department of General Surgery, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Teplyakova
authors.affiliation: Municipal Hospital Emergency Medical Care named after N.S. Karpovich, Krasnoyarsk, Russia.
authors.forename: Vera V
authors.initials: VV
authors.lastname: Kamshilova
authors.affiliation: Central Research Laboratory of Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Kotlovsky
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: Akihito
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan; Far Eastern Federal University School of Biomedicine, Vladivostok, Russia.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Reva
authors.affiliation: Research Institute of Children's Infection, 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: 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: 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: Russia-Japan Center of Microbiology, Metagenomics and Infectious Diseases, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia; Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Epidemiology, Genomics, and Evolution, International Medical Education and Research Center, Niigata, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D004269:DNA, Bacterial / Q000032:analysis; D024901:Drug Resistance, Multiple, Bacterial; D019143:Evolution, Molecular; D005260:Female; D005500:Follow-Up Studies; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000302:isolation & purification; D008875:Middle Aged; D010957:Plasmids / Q000032:analysis / Q000235:genetics; D011014:Pneumonia / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D012426:Russia; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D037521:Virulence Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D037521:Virulence Factors