Laboratorio de Bioinformática y Biología Molecular. Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martín de Porras, 31, Lima, Peru.
Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe St., Room 5515, Baltimore, MD, 21205, USA.
BMC Genomics. 2017 Oct 11;18(1):769. doi: 10.1186/s12864-017-4146-z.
Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear.
We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion.
These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets.
结核病（TB）是一个全球性的主要健康问题，耐药性使控制这种疾病的努力受到了影响。吡嗪酰胺（PZA）是一种在一线和二线治疗方案中都使用的重要药物。然而，其完整的作用机制和耐药性仍不清楚。
我们对从秘鲁的非相关结核病患者中分离出来的 68 株结核分枝杆菌进行了全基因组基因分型和测序。 spoligotyping 未证实菌株的聚类模式。我们分析了 PZA 耐药性与非同义突变和特定基因之间的关联。我们发现，在没有 pncA 突变的菌株中，pncA 基因和与 PZA 耐药性显著相关的新基因发生了突变。这些基因与金属离子的运输、pH 值调节和免疫系统逃避有关。
这些结果表明了可能存在与其他人群中不同的 PZA 耐药机制，支持了 PZA 的抗菌活性可能针对多个靶点。
