Efflux pumps are membrane protein complexes conserved in all living organisms. Beyond being involved in antibiotic extrusion in several bacteria, efflux pumps are emerging as relevant players in pathogen-host interactions. We have investigated on the possible role of the efflux pump network in Shigella flexneri , the etiological agent of bacillary dysentery. We have found that S . flexneri has retained 14 of the 20 pumps characterized in Escherichia coli and that their expression is differentially modulated during the intracellular life of Shigella . In particular, the emrKY operon, encoding an efflux pump of the Major Facilitator Superfamily, is specifically and highly induced in Shigella -infected U937 macrophage-like cells and is activated in response to a combination of high K + and acidic pH, which are sensed by the EvgS/EvgA two-component system. Notably, we show that following S . flexneri infection, macrophage cytosol undergoes a mild reduction of intracellular pH, permitting EvgA to trigger the emrKY activation. Finally, we present data suggesting that EmrKY is required for the survival of Shigella in the harsh macrophage environment, highlighting for the first time the key role of an efflux pump during the Shigella invasive process.

Tripartite motif (TRIM) proteins have been shown to play important roles in cancer development and progression by modulating cell proliferation or resistance from cell death during non-homeostatic stress conditions found in tumor micro-environments. In this study, we set out to investigate the importance for cellular fitness of the virtually uncharacterized family member TRIM52.The human TRIM52 gene has arisen recently in evolution, making it unlikely that TRIM52 is required for basic cellular functions in normal cells. However, a recent genome-wide ablation screening study has suggested that TRIM52 may be essential for optimal proliferation or survival in certain genetic cancer backgrounds. Identifying genes which fit this concept of genetic context-dependent fitness in cancer cells is of interest as they are promising targets for tumor-specific therapy.We report here that TRIM52 ablation significantly diminished the proliferation of specific glioblastoma cell lines in cell culture and mouse xenografts by compromising their cell cycle progression in a p53-dependent manner. Together, our findings point to a non-redundant TRIM52 function that is required for optimal proliferation.