vanA 유전자를 지닌 Vancomycin 내성 장구균의 VanB 표현형 발현 기전
Mechanism of VanB Phenotype in Vancomycin-Resistant Enterococci carrying vanA gene
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배경 : 최근 일본, 중국 및 한국에서 teicoplanin에 감수성인vanA 유전형 vancomycin 내성 장구균(VRE)이 보고되었다. 그기전으로 vanS domain의 3점 돌연변이와 부단백인 VanY 혹은VanZ의 결여로 보고된 바 있다. 본 연구에서는 Tn 1546의 분 석을 통하여 한국에서의 VanB phenotype- vanA genotype VRE의 분자생물학적 기전을 밝히고자 하였다.방법 : 2001년부터 2004년까지 전국에 산재한 8개 대학병원에서분리된 VanB phenotype- vanA genotype Enterococcus faeci-um 28균주를 대상으로 하였다. Tn1546의 구조 분석을 위해 PCR을 시행하였고, 정제된 PCR 산물을 이용하여 염기서열분석을 하였다.결과 : 총 28균주의 VanB phenotype- vanA genotype VRE모두에서 vanS domain의 점 돌연변이가 관찰되지 않았지만 vanY유전자의 부분 혹은 완전 결실이 관찰되었다. 이 중 13균주에서vanZ 유전자의 결실이 동반되었다. 또한 2균주에서 vanX의 끝인접부분의 염기 손실이 확인되었다.
Abstract
Background : Recently, vancomycin-resistant enterococci (VRE) with the vanA genotype that are susceptible to teicoplanin have been described in Japan, Taiwan, and Korea. The investigators suggestedthree point mutations in the putative sensor domain of vanS or impairment of accessory proteins VanY and VanZ as an explanation for the VanB phenotype-vanA genotype VRE. In this study, we analyzed Tn1546-like elements to determine the molecular mechanisms responsible for the impaired glycopeptide resistance of clinical VRE isolates with VanB phenotype-vanA genotype from Korea. Methods : From 2001 to 2004, 28 clinical isolates of Enterococcus faecium with VanB phenotypevanA genotype were collected from 8 different university hospitals in diverse geographic areas in Korea. For structural analysis of Tn1546-like elements, PCR amplifications for internal regions of Tn1546 were performed. The purified PCR products were directly sequenced with an ABI Prism 3100 DNA sequencer. Results : The sequence data of the vanS regulatory gene revealed that none of the isolates had any point mutations in this gene. All 28 isolates had a complete or incomplete deletion of vanYgene. Of these, 13 strains represented a complete deletion of vanZ, and 2 strains showed the deletion of nucleotides near the end point of vanX. Conclusions : The mechanism of VanB phenotype-vanA genotype in VRE isolates from Korea is not point mutations of vanSbut the rearrangements of vanX, vanYand vanZ. (Korean J Lab Med 2006;26: 412-7)
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