NapR Regulates the Expression of Phosphoserine Aminotransferase SerC to Modulate Biofilm Formation and Resistance to Serine Stress of Mycobacteria.

is a formidable pathogen capable of establishing persistent infections within macrophages. To survive and thrive within the host environment, it has evolved intricate regulatory networks, including a diverse array of transcription factors that enable adaptation to various stresses encountered within the host. However, the mechanisms by which transcription factors regulate biofilm formation in remain incompletely understood. This study aimed to investigate the role of , encoding phosphoserine aminotransferase, and its regulation by NapR, a transcription factor, in mycobacterial physiology. NapR regulates through directly binding to its promoter. Notably, the regulatory effect and corresponding phenotypes vary due to distinct binding affinities of NapR for the promoter in different mycobacterial species. In , NapR positively regulates biofilm formation, growth on solid media, and the transition from microcolonies to microcolonies by activating . In the , on the contrary, NapR represses , thus negatively regulating colony size and alleviating the growth inhibition caused by high concentrations of serine. Furthermore, proteomic analysis suggested NapR serves as a global transcriptional regulator in strains by simultaneously modulating four metabolic pathways. These findings underscore the complex and strain-specific regulatory mechanisms governing serine metabolism in mycobacteria and provide valuable insights into the interplay between metabolism, gene regulation, and bacterial physiology.