Mitochondrial toxicity induced by oxazolidinone antibiotics : insights from studies in human cell lines and primary cells

Oxazolidinones cause rare but severe adverse effects in patients receiving prolonged treatment with these antibiotics. One of them is thrombocytopenia. The aim of the thesis was to better understand the cellular and biochemical mechanisms of this toxicity. In this context, we compared linezolid, the first drug marketed in this class, with a new, more active derivative, tedizolid. Focusing our work on mitochondria, we demonstrated that both antibiotics inhibited the synthesis of proteins encoded by the mitochondrial genome and studied the functional consequences of this inhibition on mitochondrial metabolism and ultrastructure in human cultured cells exposed to clinically relevant concentrations of both drugs. We also investigated the effects of oxazolidinones on the differentiation process of platelets precursors.