Abstract
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a major concern worldwide. In the United States, ST8 CA-MRSA with SCCmecIVa (USA300) has been predominant, affecting the entire United States. In this study, we investigated Japanese ST8 CA-MRSA with new SCCmecIVl (designated ST8 CA-MRSA/J), which has emerged in Japan since 2003. Regarding community spread and infections, ST8 CA-MRSA/J spread in 16.2–34.4% as a major genotype in the community in Japan, and was associated with skin and soft tissue infections (SSTIs), colitis, and invasive infections (sepsis, epidural abscesses, and necrotizing pneumonia), including influenza prodrome cases and athlete infections, similar to USA300. It spread to even public transport and Hong Kong through a Japanese family. Regarding genetic diversity, ST8 CA-MRSA/J included ST and spa variants and was classified into at least three pulsed-field gel electrophoresis types, ST8 Jα to γ. Of those, ST8 Jβ was associated with severe invasive infections. As for genomics, ST8 CA-MRSA/J showed high similarities to USA300, but with marked diversity in accessory genes; e.g., ST8 CA-MRSA/J possessed enhanced cytolytic peptide genes of CA-MRSA, but lacked the Panton–Valentine leukocidin phage and arginine catabolic mobile element, unlike USA300. The unique features of ST8 CA-MRSA/J included a novel mosaic SaPI (designated SaPIj50) carrying the toxic shock syndrome toxin-1 gene with high expression; the evolution included salvage (through recombination) of hospital-acquired MRSA virulence. The data suggest that ST8 CA-MRSA/J has become a successful native clone in Japan, in association with not only SSTIs but also severe invasive infections (posing a threat), requiring attention.
Similar content being viewed by others
References
Zetola N, Francis JS, Nuermberger EL, Bishai WR. Community-acquired meticillin-resistant Staphylococcus aureus: an emerging threat. Lancet Infect Dis. 2005;5:275–86.
Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet. 2006;368:874–85.
Noto MJ, Kreiswirth BN, Monk AB, Archer GL. Gene acquisition at the insertion site for SCCmec, the genomic island conferring methicillin resistance in Staphylococcus aureus. J Bacteriol. 2008;190:1276–83.
Yamamoto T, Nishiyama A, Takano T, Yabe S, Higuchi W, Razvina O, et al. Community-acquired methicillin-resistant Staphylococcus aureus: community transmission, pathogenesis, and drug resistance. J Infect Chemother. 2010;16:225–54.
Diep BA, Otto M. The role of virulence determinants in community-associated MRSA pathogenesis. Trends Microbiol. 2008;16:361–9.
Diep BA, Stone GG, Basuino L, Graber CJ, Miller A, des Etages SA, et al. The arginine catabolic mobile element and staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA300 clone of methicillin-resistant Staphylococcus aureus. J Infect Dis. 2008;197:1523–30.
Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, Heffernan H, et al. Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton–Valentine leukocidin genes: worldwide emergence. Emerg Infect Dis. 2003;9:978–84.
Labandeira-Rey M, Couzon F, Boisset S, Brown EL, Bes M, Benito Y, et al. Staphylococcus aureus Panton–Valentine leukocidin causes necrotizing pneumonia. Science. 2007;315:1130–3.
Löffler B, Hussain M, Grundmeier M, Bruck M, Holzinger D, Varga G, et al. Staphylococcus aureus Panton–Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PLoS Pathog. 2010;6:e1000715.
Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet. 2006;367:731–9.
Takizawa Y, Taneike I, Nakagawa S, Oishi T, Nitahara Y, Iwakura N, et al. A Panton–Valentine leucocidin (PVL)-positive community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strain, another such strain carrying a multiple-drug resistance plasmid, and other more-typical PVL-negative MRSA strains found in Japan. J Clin Microbiol. 2005;43:3356–63.
Shi D, Higuchi W, Takano T, Saito K, Ozaki K, Takano M, et al. Bullous impetigo in children infected with methicillin-resistant Staphylococcus aureus alone or in combination with methicillin-susceptible S. aureus: analysis of genetic characteristics, including assessment of exfoliative toxin gene carriage. J Clin Microbiol. 2011;49:1972–4.
Ho PL, Cheung C, Mak GC, Tse CW, Ng TK, Cheung CH, et al. Molecular epidemiology and household transmission of community-associated methicillin-resistant Staphylococcus aureus in Hong Kong. Diagn Microbiol Infect Dis. 2007;57:145–51.
Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, et al. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA. 2007;298:1763–71.
Iwao Y, Yabe S, Takano T, Higuchi W, Nishiyama A, Yamamoto T. Isolation and molecular characterization of methicillin-resistant Staphylococcus aureus (MRSA) from public transport. Microbiol Immunol. 2012;56:76–82.
Shibuya Y, Hara M, Higuchi W, Takano T, Iwao Y, Yamamoto T. Emergence of the community-acquired methicillin-resistant Staphylococcus aureus USA300 clone in Japan. J Infect Chemother. 2008;14:439–41.
Yabe S, Takano T, Higuchi W, Mimura S, Kurosawa Y, Yamamoto T. Spread of the community-acquired methicillin-resistant Staphylococcus aureus USA300 clone among family members in Japan. J Infect Chemother. 2010;16:372–4.
Mine Y, Higuchi W, Taira K, Nakasone I, Tateyama M, Yamamoto T, et al. Nosocomial outbreak of multidrug-resistant USA300 methicillin-resistant Staphylococcus aureus causing severe furuncles and carbuncles in Japan. J Dermatol. 2011;38:1167–71.
Yamamoto T, Takano T, Yabe S, Higuchi W, Iwao Y, Isobe H, et al. Super-sticky familial infections caused by Panton–Valentine leukocidin-positive ST22 community-acquired methicillin-resistant Staphylococcus aureus in Japan. J Infect Chemother 2012 (in press).
Takano T, Higuchi W, Otsuka T, Baranovich T, Enany S, Saito K, et al. Novel characteristics of community-acquired methicillin-resistant Staphylococcus aureus strains belonging to multilocus sequence type 59 in Taiwan. Antimicrob Agents Chemother. 2008;52:837–45.
Higuchi W, Hung WC, Takano T, Iwao Y, Ozaki K, Isobe H, et al. Molecular characteristics of the Taiwanese multiple drug-resistant ST59 clone of Panton–Valentine leucocidin-positive community-acquired methicillin-resistant Staphylococcus aureus from pediatric cellulitis. J Infect Chemother. 2010;16:144–9.
Yamamoto T, Dohmae S, Saito K, Otsuka T, Takano T, Chiba M, et al. Molecular characteristics and in vitro susceptibility to antimicrobial agents, including the des-fluoro(6) quinolone DX-619, of Panton–Valentine leucocidin-positive methicillin-resistant Staphylococcus aureus isolates from the community and hospitals. Antimicrob Agents Chemother. 2006;50:4077–86.
International Working Group on the Classification of Staphylococcal Cassette Chromosome Elements. Classification of staphylococcal cassette chromosome mec (SCCmec): guidelines for reporting novel SCCmec elements. Antimicrob Agents Chemother. 2009;53:4961–7.
Iwao Y, Takano T, Higuchi W, Yamamoto T. A new staphylococcal cassette chromosome mec IV encoding a novel cell-wall-anchored surface protein in a major ST8 community-acquired methicillin-resistant Staphylococcus aureus clone in Japan. J Infect Chemother 2012 (in press).
Li M, Cheung GY, Hu J, Wang D, Joo HS, Deleo FR, et al. Comparative analysis of virulence and toxin expression of global community-associated methicillin-resistant Staphylococcus aureus strains. J Infect Dis. 2010;202:1866–76.
Clinical and Laboratory Standards Institute. Performance standard for antimicrobial susceptibility testing; 21st informational supplement. M100-S21. Wayne: Clinical and Laboratory Standards Institute; 2011.
Ladhani S, Joannou CL, Lochrie DP, Evans RW, Poston SM. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev. 1999;12:224–42.
Yamaguchi T, Yokota Y, Terajima J, Hayashi T, Aepfelbacher M, Ohara M, et al. Clonal association of Staphylococcus aureus causing bullous impetigo and the emergence of new methicillin-resistant clonal groups in Kansai district in Japan. J Infect Dis. 2002;185:1511–6.
Redziniak DE, Diduch DR, Turman K, Hart J, Grindstaff TL, MacKnight JM, et al. Methicillin-resistant Staphylococcus aureus (MRSA) in the athlete. Int J Sports Med. 2009;30:557–62.
Takesue Y, Yokoyama T, Kodama T, Santou T, Nakamitsu A, Murakami Y, et al. Toxin involvement in methicillin-resistant Staphylococcus aureus enteritis in gastroenterological surgery. Gastroenterol Jpn. 1991;26:716–20.
Hidron AI, Low CE, Honig EG, Blumberg HM. Emergence of community-acquired meticillin-resistant Staphylococcus aureus strain USA300 as a cause of necrotising community-onset pneumonia. Lancet Infect Dis. 2009;9:384–92.
Savolainen K, Paulin L, Westerlund-Wikström B, Foster TJ, Korhonen TK, Kuusela P. Expression of pls, a gene closely associated with the mecA gene of methicillin-resistant Staphylococcus aureus, prevents bacterial adhesion in vitro. Infect Immun. 2001;69:3013–20.
Dedent AC, Marraffini LA, Schneewind O. Staphylococcal sortase and surface proteins. In: Fischetti VA, Novick RP, Fischetti JJ, Potnoy DA, Rood JI, editors. Gram-positive pathogens. 2nd ed. Washington, DC: American Society for Microbiology; 2006. p. 486–95.
Novick RP, Christie GE, Penadés JR. The phage-related chromosomal islands of gram-positive bacteria. Nat Rev Microbiol. 2010;8:541–51.
Shittu AO, Udo EE, Lin J. Insights on virulence and antibiotic resistance: a review of the accessory genome of Staphylococcus aureus. Wounds. 2007;19:237–44.
Novick RP. Mobile genetic elements and bacterial toxinoses: the superantigen-encoding pathogenicity islands of Staphylococcus aureus. Plasmid. 2003;49:93–105.
Lappin E, Ferguson AJ. Gram-positive toxic shock syndromes. Lancet Infect Dis. 2009;9:281–90.
Orii KO, Iwao Y, Higuchi W, Takano T, Yamamoto T. Molecular characterization of methicillin-resistant Staphylococcus aureus from a fatal case of necrotizing fasciitis in an extremely low-birth-weight infant. Clin Microbiol Infect. 2010;16:289–92.
Wang R, Braughton KR, Kretschmer D, Bach TH, Queck SY, Li M, et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med. 2007;13:1510–4.
Edwards AM, Potts JR, Josefsson E, Massey RC. Staphylococcus aureus host cell invasion and virulence in sepsis is facilitated by the multiple repeats within FnBPA. PLoS Pathog. 2010;6:e1000964.
Jönsson K, McDevitt D, McGavin MH, Patti JM, Höök M. Staphylococcus aureus expresses a major histocompatibility complex class II analog. J Biol Chem. 1995;270:21457–60.
Kobayashi SD, DeLeo FR. An update on community-associated MRSA virulence. Curr Opin Pharmacol. 2009;9:545–51.
Rouch DA, Byrne ME, Kong YC, Skurray RA. The aacA-aphD gentamicin and kanamycin resistance determinant of Tn4001 from Staphylococcus aureus: expression and nucleotide sequence analysis. J Gen Microbiol. 1987;133:3039–50.
Acknowledgments
We thank Jerome Etienne, L.K. McDougal, and L.L. McDonald for MRSA reference strains and Kohei Akazawa for statistical analysis.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Iwao, Y., Ishii, R., Tomita, Y. et al. The emerging ST8 methicillin-resistant Staphylococcus aureus clone in the community in Japan: associated infections, genetic diversity, and comparative genomics. J Infect Chemother 18, 228–240 (2012). https://doi.org/10.1007/s10156-012-0379-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10156-012-0379-6