Abstract：
Pyrazinamide plays an important role in the treatment of tuberculosis. However, the microbiological test for pyrazinamide resistance is more complex and less reliable than testing of susceptibility to other anti-tuberculosis drugs due to the need to grow the pathogen at pH 5.5. Identification of mutations that cause resistance to anti-tuberculosis drugs can replace microbiological methods. Mutations in the pncA gene are responsible for the main mechanism of the resistance to pyrazinamide and are found in more than 90% of resistant strains. However, the genetic method for determining drug susceptibility is very complex, because mutations leading to pyrazinamide resistance are diverse and scattered throughout the gene. We have developed a software package for automatic data interpretation and prediction of the resistance to pyrazinamide based on Sanger sequencing results. The effectiveness of detection of pyrazinamide resistance in 16 clinical samples was compared using the BACTEC MGIT 960 automated system and pncA gene Sanger sequencing with automated analysis of the results. A significant advantage of the developed method over a single microbiological study was shown, due to greater reliability of the results irrespective of the purity of isolates.
摘要：
吡嗪酰胺在结核病的治疗中起着重要作用。然而,吡嗪酰胺耐药性的微生物学试验比其他抗结核药物敏感性试验更复杂,可靠性也更低,因为需要在pH5.5时培养病原体.鉴定引起抗结核药物耐药性的突变可以替代微生物学方法。pncA基因的突变是吡嗪酰胺抗性的主要机制，在90％以上的抗性菌株中发现。然而,确定药物敏感性的遗传方法非常复杂，因为导致吡嗪酰胺抗性的突变是多种多样的，并且分散在整个基因中。我们开发了一个软件包，用于根据Sanger测序结果自动数据解释和预测吡嗪酰胺耐药性。使用BACTECMGIT960自动系统和pncA基因Sanger测序与结果的自动分析比较了16个临床样品中吡嗪酰胺耐药性检测的有效性。已开发的方法比单个微生物研究具有显着的优势，由于无论分离物的纯度如何，结果的可靠性更高。
