Shortening of Amino Acids from C-terminal of PZase as Basis of Pyrazinamide Resistance in P14 Isolate of Mycobacterium tuberculosis Strain

摘要

Pyrazinamide (PZA) is one of the mainstays WHO-recommended drugs for therapy of tuberculosis (TB). The emergence of PZA resistance in clinical isolates of M. tuberculosis is often associated with pncA gene mutations encoding PZase. A local clinical isolate of Mycobacterium tuberculosis strain showed phenotipe resistant to PZA at concentration of 10 μg/mL. The ORF of pncA gene of the isolate showed deletion of guanine base at position 81, then followed by shortening of 70 amino acids from C-terminal of PZAse which has 186 amino acid residues. The mutant of PZase took frame shift of amino acids after the residue at position 27. The pncA gene mutation at the level of genotype, that produced a physical-chemical alteration of the active site or the metal-binding site of PZase, in this case perturbing or lossing its activity was proposed as trigering the PZA resistance in P14 clinical isolate of M. tuberculosis strain.