Identification of the mechanisms of resistance and potential cross resistance of Listeria monocytogenes upon adaptation to different antimicrobials

Abstract

ACKNOWLEDGMENTSI would like to thank Dr. Vera Katić for being my mentor, not only through PhD studies, but in my undergraduate years as well. Her objectivity, articulate thinking and dedication to work inspired me to keep moving forward even after long, tiresome days in the lab. I will forever appreciate Dr. Katic's encouragement to pursue personal happiness and her support in important life decisions.I am forever grateful to Dr. Sophia Kathariou for accepting me in her lab and making me feel at home while far from it. Her incredible ability to find the best solutions when things were not looking promising and open completely new horizons along with her creativity and knowledge made science so attractive. Looking at all the great, bright and skilful young people pursuing their dreams under Dr. Kathariou's guidance makes me very proud for being a part of it.My appreciation also goes to Dr. Lepšanović and Dr. Mišić for accepting to be members of the committee. I am thankful to all my lab mates and to Ms. Robin Siletzky for her solid support throughout my work. A special thanks to Dr. Vikrant Dutta for his patience, willingness to help and his much admired teaching skills.Lastly and foremost I would like to thank my family. To my dear parents Ljubo and Zora whose unconditional love, support and presence whenever I needed them have been and will always be my motive to be better. To my big brother Zoran, who has been, and is my role model, but still owes me German lessons. Finally, I want to thank my boys, my beloved husband Sergio and my precious son Gregory, who have been an endless source of energy, support and love. Thanks for being my wingmen guys! ABSTRACTAbility to contaminate ready-to-eat, highly processed, cold-stored food products, relatively high fatality rate and environmental adaptations define .Listeria monocytogenes as a challenging foodborne pathogen of high public health significance. Listeria's adaptations and prolonged persistence in food processing facilities are a key link to contamination of foods.In recent years, bacterial multidrug resistance has been recognized as an emerging health challenge. Exposure to antimicrobials (antibiotics, disinfectants or environmentally ubiquitous heavy metals), may provide selective pressures for resistance with accompanying cross-resistance and increase in environmental fitness.In this work I addressed some of the possible mechanisms of adaptations that may contribute to persistence of L. monocytogenes in the environment as well as to survival and growth in different foods. This includes adaptations to heavy metals such as cadmium, disinfectants such as benzalkonium chloride (BC), selected antibiotics (e.g. the fluoroquinolone ciprofloxacin) and other toxic compounds (e.g. tetraphenyl-phosponium, often used as an anti-carcinogenic and efflux pump substrate). In order to characterize the impact of multidrug resistance on survival and growth of L. monocytogenes in different foods, we tested mutants adapted to higher concentrations of antibiotic ciprofloxacin and ...