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oprD, gyrA 및 parC 유전자에 변이를 갖는 Carbapenem 내성 녹농균

Chromosomal Mutations in oprD, gyrA, and parC in Carbapenem Resistant Pseudomonas aeruginosa

조혜현|구선회|성지연|권계철
대한임상미생물학회 (Korean Society of Clinical Microbiology)|2011.12|Annals of Clinical Microbiology|제14권 제4호|pp. 131-137

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키워드

Carbapenem resistant P. aeruginosaOprDEfflux system regulatory proteinsQRDR

초록

배경: Carbapenem 내성 녹농균의 확산은 이 균에 의한 감염증 치료에 많은 어려움을 준다. 본 연구에서는 녹농균의 carbapenem 내성기전을 분석하기 위해 OprD 및 유출펌프 조절유전자(MexR, NalC, NalD, MexT 및 MexZ)의 염색체상의 변이를 조사하였다. 아울러 quinolone 내성기전을 알아보기 위해 QRDR (quinolone resistance-determining region) 변이도 함께 조사하였다. 방법: Repetitive extragenic palindromic sequence-based PCR (rep-PCR)을 이용하여 서로 다른 클론에 속하는 녹농균을 선별하였다. 총 21주가 서로 밴드 패턴을 보였으며 이 균주들을 대상으로 PCR과 DNA 염기서열분석을 통해 β-lactamase 유전자를 검출하였고 유출펌프 조절유전자, oprD 및 QRDR (gyrA, gyrB, parC 및 parE)의 변이를 확인하였다. 결과: 분리된 21주의 녹농균 중 한 주(P28)가 blaVIM-2를 가지고 있었으며 2주가 nalD 또는 mexZ에 유출펌프의 과량발현을 유발할 수 있는 변이를 가지고 있었다. OprD의 소실을 유발할 수 있는 염색체상의 변이가 21주의 녹농균 중 4주에서확인되었다. Imipenem 및 ciprofloxacin에 내성인 녹농균 10주 중 9주가 gyrA와/또는 parC에 변이를 가지고 있었다. 결론: Carbapenem 내성 녹농균은 유출펌프의 과량발현, OprD 단백의 소실 및 carbapenemase 생성 등에 의해서 carbapenem에 내성을 나타낸다. 녹농균은 또한 gyrA와/또는 parC의 QRDR에 변이를 일으켜 quinolone에 내성을 나타낸다.

Abstract

Background: Outbreaks of carbapenem resistant P.aeruginosa give rise to significant therapeutic challenges for treating nosocomial infections. In this study, we analyzed carbapenem resistance mechanisms in carbapenem resistant and clonally different P. aeruginosa strains. We analyzed chromosomal alterations in the genes of OprD and efflux system regulatory proteins (MexR, NalC, NalD, MexT, and MexZ). We also investigated chromosomal alterations in the quinolone resistance-determining region (QRDR) for quinolone resistance mechanisms. Methods: Twenty-one clonally different P. aeruginosa strains were isolated by repetitive extragenic palindromic sequence-based PCR (rep-PCR). PCR and DNA sequencing were conducted for the detection of β-lactamase genes and chromosomal alterations of efflux pump regulatory genes, oprD, and QRDR in gyrA, gyrB, parC, and parE. Results: Only one (P28) of the 21 strains harbored blaVIM-2. Two isolates had mutations in nalD or mexZ that were associated with efflux pump overexpression. Chromosomal alterations causing loss of OprD were found in 4 out of 21 carbapenem resistant P. aeruginosa strains. Nine of 10 imipenem and ciprofloxacin resistant strains had alterations in gyrA and/or parC. Conclusion: Carbapenem resistance in P. aeruginosa was mediated by several mechanisms, including loss of the OprD, overexpression of efflux systems, and production of carbapenemase. Resistance to quinolone is frequently caused by point mutations in gyrA and/or parC.

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