Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Relationship between Moxifloxacin Resistance Pheno- and Genotype of Moxifloxacin-Resistant Mycoplasma hominis Obtained in vitro

인위적으로 유도된 목시플로사신 내성 Mycoplasma hominis의 표현형과 유전자형의 연관성

  • Park, In-Dal (Department of Microbiology Kosin University College of Medicine) ;
  • Choi, Myung-Won (Research Institute for Antimicrobial Resistance)
  • 박인달 (고신대학교 의과대학 미생물학교실) ;
  • 최명원 (항생제 내성연구소)
  • Received : 2010.08.06
  • Accepted : 2010.10.07
  • Published : 2010.10.30
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Abstract

Moxifloxacin (MF) - resistant mutants of Mycoplasma hominis (M. hominis) were generated by stepwise selection in increasing concentrations of MF, and six strains of MF resistant M. hominis mutants - M1, M4, M8, M16, M32, and M64 - in which MICs of MF were 0.5, 4, 8, 16, 32, 64 ${\mu}g$/ml, respectively, were generated. Compared to the sequence of M. hominis PG21, all mutants harbored amino acid substitutions of Arg-163 Thr in GyrA, and Pro-445 Gln in ParE. While the concentrations were getting higher, an additional amino acid substitution was found at Ser-153 Lys in GyrA (${\geq}4{\mu}g/ml$), Ser-91 Ile in ParC (${\geq}16{\mu}g/ml$), and Val-450 Phe (${\geq}64{\mu}g/ml$) in GyrB. These substitutions seem to have an impact on resistance to MF, and GyrB change was found only in the highest concentration and seems to be associated with high-level resistance to MF. This, as far as we know, is the first description of a relationship between MF resistance phenotype and genotype.

본 연구에서는 QRDRs의 유전자 돌연변이와 목시플로사신의 농도와의 관계를 알아보기 위하여 목시플로사신의 농도를 단계적으로 높여가며 Mycoplasma hominis (M. hominis)에 작용시켜 목시플로사신에 내성을 갖는 균주 6주(M1, M4, M8, M16, M32, M64)를 만들었고, 이 돌연변이주들의 MIC는 각각 0.5, 4, 8, 16, 32, 64 ${\mu}g$/ml이었다. 이 균들의 염기서열을 분석하였더니 모든 돌연변이주들에서 Arg163Thr (GyrA), Pro445Gln (ParE) 아미노산 치환이 관찰 되었고, 목시플로사신의 농도가 높아질수록 Ser153Lys (GyrA, ${\geq}4{\mu}g$/ml), Ser91Ile (ParC, ${\geq}16{\mu}g/ml$), Val450Phe (GyrB, ${\geq}64{\mu}g/ml$) 등과 같은 아미노산의 치환이 추가로 관찰되었다. 이러한 아미노산의 치환이 목시플로사신의 내성과 연관이 있는 것으로 생각되며, 특히 GyrB 단백질의 아미노산 치환은 목시플로사신의 고도 내성과 연관이 있는 것으로 생각된다.

Keywords

References

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