Jpn. J. Infect. Dis., 57, 187-188, 2004

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Laboratory and Epidemiology Communications

The Genetic Properties of Streptococcus pyogenes emm49 Genotype Strains Recently Emerged among Severe Invasive Infections in Japan

Tadayoshi Ikebe, Miyoko Endo1, Yuka Ueda2, Kyoko Okada3, Rieko Suzuki4, Takeshi Minami5, Hiroshi Tanaka6, Norihiko Nakanishi7, Masaaki Tomita8, Hiroyuki Nishie9, Noriko Ishii9, Emi Sasaki9, Yuji Miura10, Toru Yamamura10 and Haruo Watanabe*

National Institute of Infectious Diseases, Tokyo 162-8640,
1Tokyo Metropolitan Research Laboratory of Public Health, Tokyo 169-0073, 2Kinki University, Osaka 589-8511, 3Health Research Institute of the City of Kawasaki, Kawasaki 210-0834, 4Kanagawa Prefectural Public Health Laboratory, Yokohama 241-0815, 5St. Marianna University School of Medicine, Kawasaki 216-8511, 6Ehime Prefectural Institute of Public Health and Environmental Science, Ehime 790-0003, 7Ehime Prefectural Central Hospital, Matsuyama 790-0024, 8Yamaguchi Prefectural Research Institute of Public Health, Yamaguchi 753-0821, 9Hiroshima City Hospital, Hiroshima 730-8518 and 10Kawakita General Hospital, Tokyo 166-8588

Communicated by Yoshichika Arakawa

(Accepted July 20, 2004)

*Corresponding author: Mailing address: Department of Bacteriology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. Tel & Fax: +81-3-5285-1171, E-mail:

Streptococcus pyogenes (group A streptococcus; GAS) is one of the most common human pathogens. It causes a wide array of infections, the most frequent of which is acute pharyngitis (strep throat). Many streptococcal virulence factors involved in GAS-based diseases have been reported, including pyrogenic exotoxins and M protein. M protein, which is an important virulence factor of S. pyogenes, protects S. pyogenes from phagocytosis by polymorphonuclear leukocytes (1, 2). More than 90 M protein-derived serotypes have been identified, and a molecular approach to the identification of emm (M protein) genes has also been documented ( emmtypes.html). For example, emm1, emm2, and emm3 genes encode the M1, M2, and M3 proteins, respectively. emm genotyping is also a useful tool for epidemiological investigation.

Since the late 1980s, streptococcal toxic shock-like syndrome (TSLS) caused by S. pyogenes has become a serious problem in both developed and developing countries. Its characteristic symptoms progress very rapidly and are fulminant from their onset. Patients can develop necrosis of the soft tissue, acute kidney failure, adult respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), and multiorgan failure (MOF) within scores of hours, leading to shock and death. The first defined case of TSLS in Japan was reported in 1992 (3), and the strains of the emm1 genotype have been found to be dominant in causing TSLS in Japan (4). Since 2000, a total of five emm49 genotype S. pyogenes strains have been isolated from severe invasive GAS patients in Japan, but had not been isolated before 1999 (Table 1); 1 case was reported in 2000, 3 cases in 2002, and 1 case in 2003. T serotypes of all the isolates were grouped into the nontypable.

We examined whether or not five isolates carry pyrogenic exotoxin genes speA, speB, and speC, by PCR with specific primers. All of the isolates carried speB gene. None of the isolates carried speC gene. Four of five isolates had speA gene (Table 1). SmaI- or SfiI- digested pulsed field gel electrophoresis (PFGE) profiles of the isolates were examined as described previously (5). NIH200, NIH211, and NIH230 strains were isolated from the patients unrelated each other; however, their PFGE profiles were indistinguishable from one another (Fig. 1). The PFGE profiles of NIH147 and NIH226 were different in several fragments from the above strains, but their profiles as a whole seemed to be similar each other. These results suggest that clonal or possibly related strains of the recently emerged emm49 genotype S. pyogenes have been spreading to cause severe invasive diseases. Much attention should be paid to the prevalence of the strains.


  1. Hortsmann, R. D., Sievertsen, H. J., Knobloch, J. and Fischetti, V. A. (1988): Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc. Natl. Acad. Sci. USA, 85, 1657-1661.
  2. Fischetti, V. A. (1989): Streptococcal M protein: molecular design and biological behavior. Clin. Microbiol. Rev., 2, 285-300.
  3. Shimizu, Y., Ohyama, A., Kasama, K., Miyazaki, M., Ooe, K. and Ookochi, Y. (1993): Case report of toxic shock-like syndrome due to group A streptococcal infection. J. Jpn. Assoc. Infect. Dis., 67, 236-239 (in Japanese).
  4. Ikebe, T., Murai, N., Endo, M., Okuno, R., Murayama, S., Saitoh, K., Yamai, S., Suzuki, R., Isobe, J., Tanaka, D., Katsukawa, C., Tamaru, A., Katayama, A., Fujinaga, Y., Hoashi, K., Ishikawa, J., Watanabe, H. and the Working Group for Group A Streptococci in Japan (2003): Changing prevalent T serotypes and emm genotypes of Streptococcus pyogenes isolates from streptococcal toxic shock-like syndrome (TSLS) patients in Japan. Epidemiol. Infect., 130, 569-572.
  5. Ikebe, T., Wada, A., Inagaki, Y., Sugama, K., Suzuki, R., Tanaka, D., Tamaru, A., Fujinaga, Y., Abe Y., Shimizu Y., Watanabe, H. and the Working Group for Group A Streptococci in Japan (2002): Dissemination of the phage-associated novel superantigen gene speL in recent invasive and noninvasive Streptococcus pyogenes M3/T3 isolates in Japan. Infect. Immun., 70, 3227-3233.
  6. Haanes, E. J. and Cleary, P. P. (1989): Identification of a divergent M protein gene and an M protein-related gene family in Streptococcus pyogenes serotype 49. J. Bacteriol., 171, 6397-6408.

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