Innovative treatments against antibiotic-resistant and persister Klebsiella pneumoniae

Resumo

Nosocomial infections are a major global health problem, with an incidence rate already reaching 7.1% in the European Union. Data from the European Centre for Disease Prevention and Control (ECDC) estimate approximately 33,000 deaths per year in Europe as a direct consequence of infections by antibiotic-resistant bacteria. Among the most common bacterial pathogens causing difficult-to-treat infections, Klebsiella pneumoniae is included. This PhD project aims to develop innovative and effective anti-infectious treatments against antibiotic-resistant and persister K. pneumoniae, following two complementary strategies: on the one hand, innovation in the use of antibacterial therapies, such as the use of bacteriophages and the repositioning of "non-antibiotic" drugs approved by the FDA for other therapeutic indications; on the other hand, the combination of both strategies to achieve a synergistic effect. Following these premises, this doctoral thesis explores the lytic capacity of two bacteriophages against K. pneumoniae and repurposed anticancer, mucolytic and antiparasitic agents, which are evaluated in vitro and in the in vivo model of Galleria mellonella larvae in synergistic combinations, to shed some light on the treatment of K. pneumoniae infections.