Genetic analysis of pyrazinamide resistance: mutations in the pncA gene among clinical isolates of multi-drug resistant Mycobacterium Tuberculosis

Abstract

Pyrazinamide (PZA) resistance presents a significant challenge in tuberculosis (TB) management, particularly in multi-drug resistant (MDR) cases. Understanding the genetic basis of PZA resistance is crucial for effective treatment strategies. This review provides a comprehensive overview of recent advancements in molecular characterization of PZA resistance, focusing on mutations in the pncA, rpsA, and panD genes. We discuss the prevalence of PZA resistance, mechanisms of resistance, and the utility of genetic analysis in early diagnosis. Key findings from studies investigating PZA resistance in clinical isolates are summarized, highlighting the predominant role of pncA mutations. Additionally, we explore the significance of mutations in rpsA and panD genes, elucidating alternative pathways to PZA resistance. Insights from genetic analysis have implications for personalized treatment approaches and TB control programs. Future directions in research and the potential of molecular methods in enhancing PZA susceptibility testing are also discussed.