Mestdagh M, Realini L, Fonteyne P A, Rossau R, Jannes G, Mijs W, DE Smet K A, Portaels F, Van den Eeckhout E
Laboratory for Pharmaceutical Biotechnology, FFW, University of Ghent, Belgium.
Microb Drug Resist. 2000 Winter;6(4):283-7. doi: 10.1089/mdr.2000.6.283.
Mutations in the pncA gene, encoding pyrazinamidase, are considered the major mechanism of pyrazinamide (PZA) resistance in Mycobacterium tuberculosis, but resistant strains containing the wild-type gene have been described. The correlation of pncA sequence with PZA resistance level was examined for 21 M. tuberculosis clinical isolates. Susceptibility patterns were determined for 100, 300, and 900 microg/ml concentrations of the drug in BACTEC. Insertions and deletions and a substitution in the putative promoter region led to high-level resistance, whereas substitutions within the open reading frame seemed to confer variable levels of resistance. Variable resistance levels and PZase activities were also observed among isolates lacking pncA mutations. The high-level resistance (900 microg/ml) in pncA wild-type isolates highlights the clinical significance of these isolates. These data also suggest that there may still be more than one alternative mechanism leading to PZA resistance in M. tuberculosis isolates.
编码吡嗪酰胺酶的pncA基因突变被认为是结核分枝杆菌对吡嗪酰胺（PZA）耐药的主要机制，但已报道存在含有野生型基因的耐药菌株。对21株结核分枝杆菌临床分离株检测了pncA序列与PZA耐药水平的相关性。在BACTEC中测定了该药物浓度为100、300和900μg/ml时的药敏模式。推定启动子区域的插入、缺失和一个替换导致高水平耐药，而开放阅读框内的替换似乎赋予不同水平的耐药性。在缺乏pncA突变的分离株中也观察到了不同的耐药水平和吡嗪酰胺酶活性。pncA野生型分离株中的高水平耐药（900μg/ml）突出了这些分离株的临床意义。这些数据还表明，在结核分枝杆菌分离株中可能仍存在不止一种导致PZA耐药的替代机制。
