Study of tolerance, persistence and resistance mechanisms in nosocomial pathogenssearch of new treatments targets

Abstract

One of the greatest current threats to public health is the rapid increase in the emergence of antibiotic resistant strains of bacteria. This increase is due to multiple factors, including the development of tolerant and/or persistent populations under stress conditions (e.g. antimicrobial treatment). The present thesis reports research investigating several molecular mechanisms of bacterial persistence and/or tolerance, particularly the quorum network (sensing/quenching) and toxin-antitoxin systems (TA), in both clinical and environmental isolates. In relation to the quorum network, we carried out genomic and expression studies with an airborne strain isolated from a hospital environment, Acinetobacter sp. 5- 2AC02 (closely related to A. towneri), and subjected to different stress conditions. We identified the acetoin metabolism cluster and characterized the negative regulator, AcoN protein. We then investigated the importance of the quorum network in clinical isolates of Acinetobacter baumannii in the development of secondary bacteraemia following pneumonia. Finally, we carried out functional characterization studies and examined toxinantitoxin (TA) systems (such as AbkB/AbkA among others) in strains of A. baumannii and Escherichia coli.