Acinetobacter baumannii is a bacterium that causes life-threatening infections in immunocompromised patients during prolonged hospital stays. This bacterium employs several virulence factors, including outer membrane vesicles (OMVs), which are pinched off from its cell envelope. Unfortunately, infections caused by A. baumannii are very difficult to treat, because the bacterium has a strong tendency to acquire resistance against multiple antibiotics. As a result, the World Health Organization regards A. baumannii as a top-priority pathogen for the development of new antibiotics. Achieving this objective requires a better understanding of the mechanisms that A. baumannii uses to acquire resistance. In particular, mobile genetic elements (MGEs), like prophages and plasmids, as well as OMVs may promote the exchange of genetic material between bacteria. The PhD research of Rodrigo Pimenta de Oliveira Monteiro presented in this thesis was focused on understanding how these different factors determine antimicrobial resistance and virulence in A. baumannii.
Firstly, a new bioinformatics tool was developed, which allows the detection and automated analysis of prophages in sequenced A. baumannii genomes. Next, the gene regulatory SOS response of A. baumannii was studied to understand how it impacts on both prophage induction and virulence. Lastly, the prophages and plasmids of three new extremely drug resistant A. baumannii isolates from a hospital outbreak were characterized.
Altogether, the results provide novel insights into how MGEs and OMVs drive the evolution of A. baumannii towards highly antibiotic-resistant and virulent variants. A particularly noteworthy observation was that A. baumannii OMVs can carry enzymes that effectively degrade last-resort antibiotics known as carbapenems.
