Regensburg 2019 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 5: Systems biology & gene expression and signaling

BP 5.3: Vortrag

Montag, 1. April 2019, 15:45–16:00, H11

Suppressive antibiotic interactions result from jamming in the translation cycle — •Bor Kavčič¹, Gašper Tkačik¹, and Tobias Bollenbach² — ¹IST Austria, Klosterneuburg, Austria — ²University of Cologne, Cologne, Germany

Translation - synthesis of proteins by ribosomes - is regulated by translation factors and perturbed by certain antibiotics (translation inhibitors). When antibiotics are combined, they interact diversely: the combined effects range from synergistic (combined effect is stronger) to suppressive (one of the drugs loses potency). Such drug interactions are difficult to predict and their underlying mechanisms remain unknown. We systematically measured all pairwise interactions for a set of translation inhibitors. A theoretical model based on ribosomal growth laws explained some of the interactions, but was unable to explain suppression. To further elucidate the origin of these drug interactions, we mimicked antibiotic effects on translation by externally controlling the concentration of one or several key translation factors, which revealed how antibiotic action depends on the translation bottlenecks. Furthermore, if the transition rates are modified, ribosomes can get stuck in traffic jams, leading to a decrease in translation efficiency. We interpret these experiments using a stochastic model of translation based on the TASEP. Our analysis suggests that traffic jams of ribosomes in the translation cycle are at the heart of suppressive interactions between antibiotics that target initiation and translocation.