Understanding the role of multidrug efflux pumps in Shigella

The efflux pumps represent an important and consistent group of proteins involved in transport process present in all living cells. The importance of efflux pumps in bacteria has always been associated to their ability to extrude a wide range of antibiotic, resulting in a multidrug resistance phenomenon. However, efflux pumps predate the antibiotic era suggesting that their natural role is unlikely to be related to antibiotic use. Indeed, there are now accumulating evidences that certain classes of efflux pumps can be employed by several bacterial pathogens as strategy to counteract host defense mechanisms. Shigella is a Gram-negative, pathogenic enterobacterium. It is the etiological agent for human bacillary dysentery or shigellosis which ultimately leads to severe bloody and mucous diarrhea. Most cases of shigellosis occur in developing countries, resulting in serious health problems worldwide. The highly sophisticated infectious strategy of Shigella banks on the capacity of this pathogen to invade epithelial cells and macrophages, causing the inflammatory destruction of the intestinal barrier. Several evolutionary studies have clearly demonstrated that Shigella has evolved from its commensal ancestor Escherichia coli, through several steps, which include the acquisition of a large virulence plasmid and pathogenicity islands followed by the loss of several housekeeping gene functions unnecessary or deleterious for the pathogenic lifestyle. Up to now, little is known about the expression of efflux pumps during the intracellular life of Shigella as well on their regulation in response to the host cell environment. The aim of this work is to identify the major efflux pumps in Shigella and to understand their role in vivo. The results obtained indicate that expression profile of efflux pump genes vary in response to the intracellular environment, suggesting a potential role in the adaptation of Shigella inside the host cells. In particular, our results allowed us to identify efflux pump encoding genes up- or downregulated in macrophages and epithelial cells