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

Olga E Khokhlova; Wei-Chun Hung; Tsai-Wen Wan; Yasuhisa Iwao; Tomomi Takano; Wataru Higuchi; Svetlana V Yachenko; Olga V Teplyakova; Vera V Kamshilova; Yuri V Kotlovsky; Akihito Nishiyama; Ivan V Reva; Sergey V Sidorenko; Olga V Peryanova; Galina V Reva; Lee-Jene Teng; Alla B Salmina; Tatsuo Yamamoto

doi:10.1371/journal.pone.0128017

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

PLoS One. 2015 Jun 5;10(6):e0128017. doi: 10.1371/journal.pone.0128017. eCollection 2015.

Authors

Olga E Khokhlova¹, Wei-Chun Hung², Tsai-Wen Wan³, Yasuhisa Iwao⁴, Tomomi Takano⁵, Wataru Higuchi⁵, Svetlana V Yachenko⁶, Olga V Teplyakova⁷, Vera V Kamshilova⁸, Yuri V Kotlovsky⁹, Akihito Nishiyama⁵, Ivan V Reva¹⁰, Sergey V Sidorenko¹¹, Olga V Peryanova¹², Galina V Reva¹³, Lee-Jene Teng¹⁴, Alla B Salmina¹⁵, Tatsuo Yamamoto⁴

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁶ Krasnoyarsk Regional Center for Prevention and Control of AIDS and Infectious Diseases, Krasnoyarsk, Russia.
⁷ City Clinical Hospital No. 7, Krasnoyarsk, Russia; Department of General Surgery, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
⁸ Municipal Hospital Emergency Medical Care named after N.S. Karpovich, Krasnoyarsk, Russia.
⁹ Central Research Laboratory of Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.
¹⁰ 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.
¹¹ Research Institute of Children's Infection, St. Petersburg, Russia.
¹² 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.
¹³ Far Eastern Federal University School of Biomedicine, Vladivostok, Russia.
¹⁴ Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁵ Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Professor V.F. Vojno-Yasenetsky, Krasnoyarsk, Russia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Child
Child, Preschool
Community-Acquired Infections / microbiology*
Community-Acquired Infections / mortality
Community-Acquired Infections / pathology
DNA, Bacterial / analysis
Drug Resistance, Multiple, Bacterial
Evolution, Molecular*
Female
Follow-Up Studies
Genome, Bacterial*
Genotype
Humans
Infant
Infant, Newborn
Male
Methicillin-Resistant Staphylococcus aureus / genetics*
Methicillin-Resistant Staphylococcus aureus / isolation & purification
Middle Aged
Plasmids / analysis
Plasmids / genetics
Pneumonia / microbiology*
Pneumonia / mortality
Pneumonia / pathology
Retrospective Studies
Russia
Staphylococcal Infections / microbiology*
Staphylococcal Infections / mortality
Staphylococcal Infections / pathology
Survival Analysis
Virulence Factors / genetics*
Young Adult

Substances

Bacterial Proteins
DNA, Bacterial
Virulence Factors

Grants and funding

This study was supported by a fund/grant from the Krasnoyarsk Regional Government (Russia) and Japan-Russia Youth Exchange Center (Japan), and by each institutional sources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.