Characterization of Bacterial Translation Elongation Inhibitors

Resistance to antibiotics has increased and is still growing so that almost every human pathogen has acquired resistance to at least one class of antimicrobials in clinical use. As a result, every year bacterial pathogens infect more than 1/3 of the world population causing major2 million fatalities and hospital-acquired infections in Europe account for ca.175,000 deaths. In Italy ca. 7000 deaths are caused by bacterial infections acquired by about 6.7% of hospitalized patients. The fairly large number of fatalities caused by untreatable bacterial infections in Europe in recent years further underlies the existence of an antibiotic-emergency which renders even more formidable the health threat caused by infectious diseases by both traditional pathogens and emerging superbugs. In this contest, the need for new antibiotics has increased. The aim of my work is to study the mechanisms of action of two translational inhibitors called NAI003 and HygromycinA. NAI003, is a chemical derivative of the thiopeptide GE2270A an inhibitor of bacterial elongation factor Tu (EF-Tu), while HygromycinA is an old antibiotic (discovered in the 1953) whose mechanism of action and its location on the ribosome have not yet been elucidated at least at the molecular level.