Mycobacterium tuberculosis requires riboflavin biosynthesis for survival in the host

Mycobacterium tuberculosis possesses a metabolism dependent on the flavin molecule, riboflavin, for survival within a host. This bacteria utilizes over 180 proteins that rely on flavin or deazaflavin co-factors for function. In laboratory settings, M. tuberculosis requires riboflavin biosynthesis to thrive, but this necessity is still unclear when it comes to their presence within infected host cells or tissues.

To explore this, researchers utilized a specific strain of M. tuberculosis that can conditionally express the ribA2 gene. This gene encodes an enzyme crucial for the beginning stages of riboflavin synthesis. They found that when the ribA2 gene was repressed transcriptionally, the bacteria died without any additional riboflavin supplementation.

Further analysis using RNA sequencing revealed that lack of riboflavin led to M. tuberculosis inducing a specific transcriptional profile, showing decreased activity in the electron transport chain and widespread changes to central metabolic pathways.

Moreover, when M. tuberculosis was deprived of riboflavin, it was unable to grow within cultured macrophages, the immune cells typically targeted by the bacteria. This impairment led to the detection and clearance of the bacteria from infected tissue samples in both genetically distinct mouse models, which form different types of lung lesions during infection.

The results of this study indicate that M. tuberculosis depends on the ribA2 enzyme for its survival throughout all stages of infection within a host. This dependency suggests that targeting the riboflavin biosynthesis pathway could be a promising strategy for developing new drugs to combat tuberculosis.