Chisholm Stephanie A, Owen Robert J
Helicobacter Reference Unit, Laboratory of Enteric Pathogens, Specialist and Reference Microbiology Division, Health Protection Agency, 61 Colindale Avenue, Colindale, London NW9 5HT, UK.
J Med Microbiol. 2004 Feb;53(Pt 2):135-140. doi: 10.1099/jmm.0.05342-0.
Mutations in the NAD(P)H flavin oxidoreductase gene (frxA) are thought to contribute to the development of metronidazole resistance in Helicobacter pylori. To test this further, 44 frxA sequences in 18 patient isolate sets of H. pylori were examined including a unique collection comprising separated Mtz-sensitive (MtzS) and Mtz-resistant (MtzR) subpopulations pre-treatment and matched MtzR strains post-treatment. Sequences of frxA contained frameshift mutations that led to premature protein truncation in at least one strain from most (17/18) patient sets. These mutations were present in all strains, irrespective of Mtz resistotype in 13/18 patients. Frameshift due to a single adenine deletion at nucleotide 53 was the most common mutation and was present in isolates from 11/18 patients. A novel real-time (LightCycler) PCR-based probe hybridization melting-point assay applied to a further 119 isolates confirmed that the frameshift-53 mutation occurred frequently, in 20% of isolates, and could be present in MtzS as well as MtzR strains (42% vs 58%). This study demonstrates that frameshift mutations occur in MtzS strains as well as in MtzR strains, and are thus unlikely to cause Mtz resistance.
烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）黄素氧化还原酶基因（frxA）的突变被认为与幽门螺杆菌甲硝唑耐药性的产生有关。为进一步验证这一点，研究人员检测了18组患者分离的幽门螺杆菌中的44个frxA序列，其中包括一组独特的样本，该样本包含治疗前分离的甲硝唑敏感（MtzS）和耐药（MtzR）亚群以及治疗后匹配的MtzR菌株。frxA序列中的移码突变导致了大多数（17/18）患者组中至少一个菌株的蛋白质过早截短。在13/18例患者中，无论甲硝唑耐药类型如何，所有菌株均存在这些突变。第53位核苷酸处单个腺嘌呤缺失导致的移码是最常见的突变，存在于11/18例患者的分离株中。一种基于实时（LightCycler）PCR的探针杂交熔点分析方法应用于另外119株分离株，结果证实移码53突变频繁发生，在20%的分离株中出现，并且可同时存在于MtzS和MtzR菌株中（42%对58%）。这项研究表明，移码突变在MtzS菌株和MtzR菌株中均会出现，因此不太可能导致甲硝唑耐药。
