Phd in CELL AND DEVELOPMENTAL BIOLOGY

Sepsis is one of the leading causes of death among oncology patients, mainly due to the consequences of cancer treatments, such as immune suppression and indwelling devices. In recent years a significant increase in the frequency of MDR (Multiple Drug Resistant) GNB (Gram-Negative Bacilli) has been observed, hence an early treatment with an antibiotic is fundamental for positive outcomes. The prolonged exposure to antibiotics can lead to the selection of resistant pathogens, whose emergence is increased by the DNA damaging and SOS response activating effects of chemotherapeutic compounds commonly used for cancer treatment. In addition, chemotherapeutics can deeply alter the gut microbiota composition, leading to dysbiosis and the loss of colonisation resistance. The disruption of a healthy microbiota improves the chances of multiresistant pathogens dominating the microbiota and translocating into the bloodstream, resulting in sepsis. MDR efflux pumps (EPs) are transmembrane protein transporters involved in the extrusion of toxic compounds and antibiotics that may be harmful to bacterial cells, but a rising number of evidence is being obtained about their implication in physiological roles and bacterial virulence. This project aims to investigate the contribution of transcriptional deregulation of EP genes in conferring resistance to antibiotics in bacteria exposed to therapeutic concentrations of anticancer drugs to identify targets to avoid MDR bloodstream infections in cancer patients. Parallelly, the involvement of specific EPs in the Shigella infection process will be studied to improve our knowledge of its pathogenetic mechanisms.