Transketolase of Staphylococcus aureus is involved in the control of master regulators of stress response during infection

Staphylococcus aureus is a leading cause of both acute and chronic infections in humans. The importance of the pentose phosphate pathway (PPP) during S. aureus infection is currently largely unexplored. Here, we focused on one key PPP enzyme, transketolase. We showed that inactivation of the unique gene encoding transketolase activity in S. aureus USA300 (Δtkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the Δtkt strain compared to wild-type strain in early intracellular proliferation and in the ability to colonise kidneys. Transcriptional activity of the two master regulators Sigma B and RpiRc was drastically reduced in the Δtkt mutant during host cells invasion. The concomitant increased RNAIII transcription, suggests that TKT -or a functional PPP- strongly influences the ability of S. aureus to proliferate within host cells by modulating key transcriptional regulators.