More than chromosome organizers: Unique mycobacterial nucleoid-associated proteins

Abstract

Nucleoid-associated proteins (NAPs) play a fundamental role in organizing chromosomal architecture and regulating gene expression in Mycobacterium, enabling these bacteria to adapt to diverse environments. In Mycobacterium tuberculosis (Mtb), NAPs contribute to virulence, antibiotic resistance, and persistence within the host, whereas in Mycobacterium smegmatis (Ms), they influence growth dynamics and stress responses. Recent findings indicate that, beyond their role in DNA compaction and replication, mycobacterial NAPs exert broad regulatory effects on gene expression, highlighting their significance in cellular physiology. Differences in NAP composition between saprophytic and pathogenic Mycobacterium species underscore their distinct evolutionary adaptations and survival strategies. Given their central role in bacterial homeostasis and stress adaptation, NAPs have emerged as potential targets for novel antimycobacterial therapies, particularly against drug-resistant Mtb. This review explores the structural and functional diversity of mycobacterial NAPs, emphasizing their roles in chromosomal organization, transcriptional regulation, and stress adaptation, with a focus on their implications for mycobacterial pathophysiology.