최근 국내 유입 Vibrio cholerae O1 Biotype El Tor의 특성 및 연관성 분석
Genetic Characteristics and Relatedness of Imported Vibrio cholerae O1 Biotype El Tor in Korea
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배경: 콜레라균은 수인성 설사질환의 대표적인 원인 병원체로 Vibrio cholera (V. cholerae) O1 classical형이 주요 원인 병원체였으나 제7차 대유행부터는 V. cholerae El Tor형으로 교체되어 지금까지도 유행이 지속되고 있다. 최근 전세계적으로 유행 중인 V. cholerae O1 El Tor형은 V. cholera O1 El Tor형을 기반으로 V. cholerae O1 classical형의 표현형과 유전자형의 특성을 지니고 있다. 본 연구에서는 2004년 이후 해외로부터 유입된 V. cholerae O1 ctx (+)를 대상으로 병원성 유전자의 특성 및 항균제 내성률을 조사하여 국내 콜레라 발생 대응을 위한 기반 연구를 수행하고자 하였다. 방법: 대상 균주는 2004년부터 2011년 사이에 국내로 유입된 V. cholera O1 El Tor 49주로서 PCR기법을 이용하여 ctxB 유전자와 rstR 유전자 분석을 통해 biotype 분석을 실시하였고, 항균제 감수성 검사를 통해 내성 경향을 확인하였다. 또한유전자 지문분석법(Pulsed Field-Gel Electrophoresis)을 이용하여 유입 균주 간 유전적 연관 관계를 분석하였다. 결과: 대상 균주 중 ctxB 유전자는 전부 classical형을 보였으나, rstR 유전자는 El Tor형, classical형 그리고 두 가지 biotype 을 모두 가지고 있는 균주가 확인되었다. Streptomycin, sulfamethoxazole/trimethoprim, nalidixic acid, 그리고 ciprofloxacin에내성을 보이는 균주가 20주 확인되었으며, PFGE 유형은 기존 연구를 통해 성립된 방법에 따라 확인하였을 경우 모두B그룹의 cluster로 구분되었다. 대상 균주 간 유입 시기와 혈청형에 따른 연관성은 보이지 않았으나 유입국가와 항균제내성 경향에 따른 연관관계는 높게 나왔다. 결론: 2004년 이후 해외 유입 콜레라균은 ctxB 유전자형이 classical형인 hybrid V. cholerae O1 El Tor만 분리되고 있으며, classical형 rstR 유전자만 보유하고 있는 균주 중에 rstC 유전자가 확인된 균주는 확인되지 않아 Mozambique 분리주와동일하게 CTX prophage만으로 구성된 구조를 갖고 있는 것으로 생각한다. 내성 균주에서 sxt 유전자가 확인됨으로서SXT element와 항균제 내성 관련 유전자가 연관성이 높음을 확인할 수 있었다. PFGE 유형 분석과 관련하여 항균제 내성주에 대한 연관성을 찾을 수 있어 국내 유입 콜레라균에 대한 기초 분석 자료로 활용 가치가 있을 것이다.
Abstract
Background: Cholera is a representative water-borne disease that is caused by V. cholera ctx (+). V. cholera El Tor was previously the primary pathogen, but after the seventh pandemic outbreak, it was replaced by a V. cholera El Tor variant with a classical phenotype and genotype. In this study, we investigated the genotypic and phenotypic characteristics of imported V. cholerae El Tor in Korea. Methods: Forty-nine V. cholerae O1 El Tor strains isolated from 2004 to 2011 were used in this study. Polymerase chain reaction amplification of the ctxB and rstR genes was used for biotype determination. An antimicrobial susceptibility test was performed for phenotypic analysis, and pulse field gel electrophoresis (PFGE) was used for analysis of genetic relatedness. Results: Classical ctxB genes were found in all of the isolates, while classical, El Tor, and combined rstR genes were found. Twenty strains showed antimicrobial resistance against streptomycin, sulfamethoxazole/ trimethoprim, nalidixic acid, and ciprofloxacin. Based on PFGE, all isolates were grouped as cluster B. The country of origin and resistance pattern were highly related, although the time of influx and serogroup were not. Conclusion: Isolates of V. cholera El Tor imported since 2004 were hybrids of V. cholera El Tor, which has the classical ctxB gene and is considered to be a CTX prophage. The SXT element plays an important role in antimicrobial resistance. PFGE patterns, which can be used for analysis of imported V. cholera, revealed the relatedness of the resistant isolates.
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