DosR's multifaceted role on Mycobacterium bovis BCG revealed through multi-omics

Mycobacterium tuberculosis (Mtb) is an intracellular bacterium that causes a highly contagious and potentially lethal tuberculosis (TB) in humans. It can maintain a dormant TB infection within the host. DosR (dormancy survival regulator) (Rv3133c) has been recognized as one of the key transcriptional proteins regulating bacterial dormancy and participating in various metabolic processes. In this study, we extensively investigate the still not well-comprehended role and mechanism of DosR in Mycobacterium bovis (M. bovis) Bacillus Calmette-Guerin (BCG) through a combined omics analysis. Our study finds that deleting DosR significantly affects the transcriptional levels of 104 genes and 179 proteins. Targeted metabolomics data for amino acids indicate that DosR knockout significantly upregulates L-Aspartic acid and serine synthesis, while downregulating seven other amino acids, including L-histidine and lysine. This suggests that DosR regulates amino acid synthesis and metabolism. Taken together, these findings provide molecular and metabolic bases for DosR effects, suggesting that DosR may be a novel regulatory target.

Automated summary

In this study, the role and mechanism of DosR in Mycobacterium bovis Bacillus Calmette-Guerin (BCG) were investigated using omics analysis. The results showed that deleting DosR significantly affected the transcriptional levels of genes and proteins. Targeted metabolomics data revealed that DosR knockout upregulated L-Aspartic acid and serine synthesis while downregulating seven other amino acids. These findings suggest that DosR regulates amino acid synthesis and metabolism, providing insights into its novel regulatory target.