Doctoral defence: Mariliis Hinnu "In Vitro Methods for Studying the Mechanisms of Ribosome-Targeting Antibiotics"

On 13 May at 14:15, Mariliis Hinnu will defend her doctoral thesis in biomedical technology "In Vitro Methods for Studying the Mechanisms of Ribosome-Targeting Antibiotics".

Supervisors:
Professor Tanel Tenson, University of Tartu
Professor Karin Kogermann, University of Tartu
Research Fellow Marta Putrinš, University of Tartu

Opponent:
Professor Alex J. O’Neill, University of Leeds, United Kingdom

Summary:
Protein biosynthesis, or translation, taking place in the ribosome is a fundamental life process. Therefore, bacterial ribosome is a major target for antibacterials. Due to the rapid spread of antibiotic resistance, it is important to make current pharmaceuticals and treatment schemes more efficient, as well as develop new and better ones. Before any clinical trials in humans, it is vital to test all potential drug candidates thoroughly in vitro as well as in infection models (cell and tissue culture / animal models). Classical in vitro environments are far from infection-mimicking conditions. The aim of the thesis was to develop in vitro methods, which would allow to study antibiotics in a biologically relevant environment. The thesis was focused on ribosome-targeting antibiotics.

Methods were developed in this PhD thesis to: i) measure antibiotic release from nanofibers intended for local wound therapy; ii) explain whether the addition of blood buffer component bicarbonate improves the clinical predictability of antibiotic susceptibility tests; and iii) measure the effects of antibiotics on translational fidelity in bacteria. In contrast to large differences in drug release between tested mats seen in standard release assays in liquid environment, developed semi-solid release methods revealed only minor differences between the mats. Studies of bicarbonate effect showed clearly that the antibiotic potency was affected by the pH change of the medium induced by insufficiently buffered bicarbonate. Additionally, a new fluorescence-based bacterial translational fidelity reporter system was developed, which gave new insights into translational accuracy in different strains, growth environments, including in intracellular infection model, and upon antibiotic exposure. In summary, the developed methods allow to study ribosome-targeting antibiotics more efficiently.

Defence can be followed in Zoom: https://ut-ee.zoom.us/j/9530588152?pwd=ZzgzMjY4YytzUkZ5aVRCd2pOdVNQQT09  (meeting ID: 953 058 8152, passcode: kaitsmine).