​Bacillus cereus is an ubiquitous bacterium whose natural habitat is soil. It is a human pathogen and the second leading cause of foodborne outbreaks in France. As a facultative anaerobe, it can grow in the absence of oxygen (anoxia), a condition encountered in particular after ingestion within the human intestinal tract, where it can produce numerous virulence factors.
The aim of this study was to determine how the model TSPO protein from B. cereus (BcTSPO), a homologue of mammalian TSPO, contributes to bacterial physiology under anoxic conditions. The use of anoxia makes it possible to investigate the function of TSPO from a more fundamental perspective. TSPO is a small membrane protein that is remarkably conserved throughout evolution, from bacteria to mammals, and has been studied in connection with various pathological processes, including neurodegenerative diseases and cancer. However, despite several decades of research, its physiological functions remain a matter of debate.

The authors adopted a multidisciplinary approach combining proteomic and biochemical analyses with the physiological characterization of a B. cereus strain lacking the tspO gene. They show that deletion of tspO leads to increased porphyrin accumulation, redox imbalance, and impaired bacterial growth. Analysis of the cellular proteome revealed extensive remodeling of central metabolism. In the absence of BcTSPO, there was an increase in the abundance of proteins involved in porphyrin metabolism, particularly in siroheme biosynthesis, as well as proteins involved in nitrate assimilation and respiratory nitrate reduction. The deletion also affected the homeostasis of iron, other metal ions, and phosphates. Finally, the induction of NO detoxification systems indicated increased nitrosative stress. These alterations in cellular metabolism were accompanied by substantial changes in the profile of proteins detected in the extracellular environment.

These findings support a model in which BcTSPO helps coordinate porphyrin and iron metabolism in B. cereus, thereby contributing to the balance between porphyrin biosynthesis, intracellular iron utilization, and redox homeostasis, while limiting the accumulation of potentially toxic intermediates. They also reveal that this role of BcTSPO does not depend exclusively on oxygen-related processes, supporting the hypothesis that coordination of porphyrin and iron metabolism may represent an ancient function of TSPO that has been conserved throughout evolution.

Contacts : Catherine Duport (catherine.duport@univ-avignon.fr ) ;
Jean Armengaud (jean.armengaud@cea.fr)