Genetic analysis of Helicobacter pylori clinical isolates suggests resistance to metronidazole can occur without the loss of functional rdxA

被引:27
作者
Kim, So Yeong [2 ]
Joo, Young Min [2 ]
Lee, Hak Sung [3 ]
Chung, In-Sik [3 ]
Yoo, Yun-Jung [2 ]
Merrell, D. Scott [1 ]
Cha, Jeong-Heon [2 ,4 ]
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA
[2] Yonsei Univ, Coll Dent, Dept Oral Biol, Oral Sci Res Ctr,Project BK21, Seoul 120749, South Korea
[3] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Gastroenterol, Seoul, South Korea
[4] Yonsei Univ, Grad Sch, Dept Appl Life Sci, Seoul 120749, South Korea
基金
新加坡国家研究基金会;
关键词
antibiotic resistance; FrxA; genetics; Helicobacter pylori; metronidazole; RdxA; ANTIMICROBIAL RESISTANCE; REDUCTIVE ACTIVATION; NITROIMIDAZOLE DRUGS; FRXA; SUSCEPTIBILITY; OXIDOREDUCTASE; INVOLVEMENT; MUTATIONS; SEQUENCE; STRAINS;
D O I
10.1038/ja.2008.6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Resistance to metronidazole (MTZ) in Helicobacter pylori is associated with mutations in rdxA, encoding an oxygen-insensitive NADPH nitroreductase, and mutations in frxA, encoding a NAD(P)H-flavin oxidoreductase. Despite this association, the strict correlation of MTZ resistance with mutations in rdxA or frxA is still controversial. In this study, rdxA allelic replacement was used to distinguish resistance-associated nucleotide mutations from the natural genetic diversity of H. pylori. Replacement with truncated rdxA resulted in MTZ resistance, whereas replacement with missense-mutated rdxA from resistant clinical isolates failed to yield MTZ resistance. Thus, although truncation of rdxA confers MTZ resistance in G27 H. pylori, MTZ resistance found in other clinical isolates is not due to the identified amino-acid substitutions. Three of our MTZ-resistant clinical isolates expressed functional rdxA and two of these also encoded full-length frxA. Therefore, MTZ resistance can arise in H. pylori possessing functional rdxA, suggesting that other factors are involved in MTZ resistance.
引用
收藏
页码:43 / 50
页数:8
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