Marais Armelle, Bilardi Claudio, Cantet Franck, Mendz George L, Mégraud Francis
Laboratoire de Bactériologie, Université Victor Segalen Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, France.
Res Microbiol. 2003 Mar;154(2):137-44. doi: 10.1016/S0923-2508(03)00030-5.
Metronidazole (Mtz) resistance in Helicobacter pylori has been found to be associated with mutations in rdxA, a gene encoding an oxygen-insensitive NADPH nitroreductase, and enhanced by mutations in frxA, a gene encoding a NAD(P)H-flavin oxidoreductase. The roles of these two genes in Mtz resistance in H. pylori were examined in this study. The rdxA and frxA genes were sequenced in nine pairs of strains isolated from biopsies obtained from patients before and after failed eradication treatments which included Mtz and resulted in the appearance of resistant strains. Metronidazole resistance could be explained in seven of these pairs of strains by mutations in rdxA and frxA. However, in one pair of strains, rdxA was identical in the susceptible and resistant strains, and only changes in frxA were observed; and in another pair, neither rdxA nor frxA were different in the susceptible and resistant strains. Sequencing of the upstream region of frxA and of the recA gene in the latter pair of strains did not reveal any mutations. To establish whether mutations in frxA alone could be involved in Mtz resistance, a resistant Escherichia coli strain transformed with the frxA of a Mtz susceptible H. pylori strain was rendered susceptible, and transformation with a mutated H. pylori frxA gene under the same conditions did not change the resistant E. coli phenotype. The results suggested that a Mtz resistance phenotype may arise in H. pylori without mutations in rdxA or frxA, or with mutations only in frxA.
已发现幽门螺杆菌对甲硝唑（Mtz）的耐药性与rdxA基因突变有关，rdxA是一种编码对氧不敏感的NADPH硝基还原酶的基因，而frxA基因突变会增强这种耐药性，frxA是一种编码NAD(P)H-黄素氧化还原酶的基因。本研究检测了这两个基因在幽门螺杆菌对Mtz耐药性中的作用。对9对菌株的rdxA和frxA基因进行了测序，这些菌株是从接受过包含Mtz的根除治疗但失败且出现耐药菌株的患者活检样本中分离得到的，治疗前后各取一对。在其中7对菌株中，rdxA和frxA基因突变可以解释甲硝唑耐药性。然而，在一对菌株中，rdxA在敏感菌株和耐药菌株中是相同的，仅观察到frxA有变化；在另一对菌株中，敏感菌株和耐药菌株的rdxA和frxA均无差异。对后一对菌株的frxA上游区域和recA基因进行测序未发现任何突变。为确定单独的frxA基因突变是否与Mtz耐药性有关，用Mtz敏感的幽门螺杆菌菌株的frxA转化的耐药大肠杆菌菌株变得敏感，而在相同条件下用突变的幽门螺杆菌frxA基因转化并未改变耐药大肠杆菌的表型。结果表明，幽门螺杆菌可能在rdxA或frxA无突变，或仅frxA有突变的情况下出现Mtz耐药表型。
