Napiórkowska A, Rüsch-Gerdes S, Hillemann D, Richter E, Augustynowicz-Kopeć E
Department of Microbiology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland.
The National Reference Centre for Mycobacteria, Forschungszentrim Borstel, Germany.
Int J Tuberc Lung Dis. 2014 Apr;18(4):454-60. doi: 10.5588/ijtld.13.0457.
Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug that is generally administered with isoniazid, rifampicin, ethambutol and streptomycin.
To analyse the correlation between phenotypic resistance to PZA and genotype to find out whether the great diversity in pncA mutations is epidemiologically useful in tracing the transmission of PZA-resistant Mycobacterium tuberculosis strains among patients.
The study included 71 PZA-resistant M. tuberculosis strains isolated from 62 Polish and 9 German patients. All strains were analysed using minimal inhibitory concentration value determination, pncA mutation analysis, spoligotyping, 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) and insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) fingerprinting.
In 63 isolates, 37 (88.7%) different mutations in the pncA gene were observed, 13 of which had not been previously reported; 11 molecular families with the same MIRU-VNTR and IS6110-RFLP pattern were found. The same mutation was identified in three families, while different ones were identified in the remaining families.
Mutations in the pncA gene are a major cause of PZA resistance in M. tuberculosis. pncA mutation analysis can be used to obtain valuable additional information, but should be applied with caution for epidemiological analysis.
吡嗪酰胺（PZA）是一种重要的一线抗结核药物，通常与异烟肼、利福平、乙胺丁醇和链霉素联合使用。
分析对PZA的表型耐药性与基因型之间的相关性，以确定pncA基因突变的巨大差异在追踪耐PZA结核分枝杆菌菌株在患者间传播的流行病学研究中是否有用。
该研究纳入了从62名波兰患者和9名德国患者中分离出的71株耐PZA结核分枝杆菌菌株。所有菌株均采用最低抑菌浓度值测定、pncA基因突变分析、间隔寡核苷酸分型、24位点分枝杆菌插入序列可变数目串联重复序列（MIRU-VNTR）和插入序列（IS）6110限制性片段长度多态性（RFLP）指纹图谱分析。
在63株分离株中，观察到pncA基因有37种（88.7%）不同突变，其中13种此前未被报道；发现了11个具有相同MIRU-VNTR和IS6110-RFLP模式的分子家族。在3个家族中鉴定出相同突变，其余家族鉴定出不同突变。
pncA基因突变是结核分枝杆菌对PZA耐药的主要原因。pncA基因突变分析可用于获取有价值的额外信息，但在流行病学分析中应谨慎应用。
