Transketolase of Staphylococcus aureus 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. In the current study, we focused on one key PPP enzyme, transketolase (TKT). We showed that inactivation of the unique gene encoding TKT activity in S. aureus USA300 (∆tkt) led to drastic metabolomic changes. Using time-lapse video imaging and mice infection, we observed a major defect of the ∆tkt strain compared with wild-type strain in early intracellular proliferation and in the ability to colonize kidneys. Transcriptional activity of the 2 master regulators sigma B and RpiRc was drastically reduced in the ∆tkt 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.

[Combination strategies for checkpoint inhibition: Current practices and perspectives]. / Combinaisons d'inhibiteurs de points de contrôle immunitaires en oncologie : état de l'art et perspectives.

T-cell checkpoint blockade therapies have revolutionized treatment protocols and prognosis in patients with cancer. Pointed out by the success of PD-1 (programmed cell death-1) plus CTLA-4 (cytotoxic-T-lymphocyte associated antigen 4) blockade in patients with melanoma, the perspective of new synergistic immunotherapy combinations seems to be an important opportunity to improve outcomes for patients. In this article, we first focus on immunotherapy combinations that have shown their efficiency and that are currently approved in solid tumors. Then, we present a summary of emerging targets with reported pre-clinical efficacy and currently evaluated through ongoing clinical trials and other immunomodulatory molecules in the tumor microenvironment.