With the rise of bacterial resistance to conventional antibiotics, re-purposing of Food and Drug Administration (FDA) approved drugs currently used to treat non-bacteria related diseases as new leads for antibacterial drug discovery has become an attractive alternative. Ethoxzolamide (EZA), an FDA-approved diuretic acting as a human carbonic anhydrase inhibitor, is known to kill the gastric pathogenic bacterium Helicobacter pylori in vitro via an, as yet, unknown mechanism. To date, EZA activity and resistance have been investigated for only one H. pylori strain, P12. We have now performed a susceptibility and resistance study with H. pylori strains SS1 and 26695. Mutants resistant to EZA were isolated, characterized and their genomes sequenced. Resistance-conferring mutations were confirmed by backcrossing the mutations into the parent strain. As with P12, resistance to EZA in strains SS1 and 26695 does not develop easily, since the rate of spontaneous resistance acquisition was less than 10-8. Acquisition of resistance was associated with mutations in 3 genes in strain SS1, and in 6 different genes in strain 26695, indicating that EZA targets multiple systems. All resistant isolates had mutations affecting cell wall synthesis and control of gene expression. EZA's potential for treating duodenal ulcers has already been demonstrated. Our findings suggest that EZA may be developed into a novel anti-H. pylori drug.

中文翻译：

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乙氧唑胺对幽门螺杆菌SS1和26695的抗菌活性。

随着细菌对常规抗生素的耐药性的提高，食品和药物管理局（FDA）批准的用于治疗非细菌性相关疾病的药物的重新用途已成为一种有吸引力的替代药物。已知乙醇乙氧胺（EZA）是一种FDA批准的利尿剂，可作为人的碳酸酐酶抑制剂，可通过一种未知的机制在体外杀死胃病菌幽门螺杆菌。迄今为止，仅对一种幽门螺杆菌菌株P12进行了EZA活性和抗性研究。现在，我们对幽门螺杆菌SS1和26695菌株进行了敏感性和耐药性研究。分离出了对EZA耐药的突变体，进行了表征并对其基因组进行了测序。通过使突变回交到亲本菌株中来确认赋予抗性的突变。与P12一样，由于自发抗性获得率低于10-8，因此菌株SS1和26695对EZA的抗性不容易发展。抗性的获得与菌株SS1中的3个基因以及菌株26695中的6个不同基因的突变相关，表明EZA靶向多个系统。所有抗性分离株都有影响细胞壁合成和基因表达控制的突变。EZA具有治疗十二指肠溃疡的潜力。我们的发现表明，EZA可能会发展成为一种新型的抗H抗体。幽门螺杆菌药物。表示EZA针对多个系统。所有抗性分离株都有影响细胞壁合成和基因表达控制的突变。EZA具有治疗十二指肠溃疡的潜力。我们的发现表明，EZA可能会发展成为一种新型的抗H抗体。幽门螺杆菌药物。表示EZA针对多个系统。所有抗性分离株都有影响细胞壁合成和基因表达控制的突变。EZA具有治疗十二指肠溃疡的潜力。我们的发现表明，EZA可能会发展成为一种新型的抗H抗体。幽门螺杆菌药物。