Cytokinin Signaling in Mycobacterium tuberculosis

It was reported the human-exclusive pathogen Mycobacterium (M.) tuberculosis secretes cytokinins, which previously had only been known as plant hormones. Cytokinins are adenine-based signaling molecules in plants that have never been shown to participate in signal transduction in other kingdoms of life. Here, we show that cytokinins induce the strong expression of the M. tuberculosis gene, Rv0077c. We found that a TetR-like transcriptional regulator, Rv0078, directly repressed expression of the Rv0077c gene. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of M. tuberculosis. Although acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice. Collectively, these findings show cytokinins signal transcriptional changes that affect the M. tuberculosis cell envelope, and that cytokinin signaling is no longer limited to the kingdom plantae.