On August 26, 2019 Tamara Milosevic (Pharmacologie cellulaire et moléculaire; promotor Prof. F. Van Bambeke) defended her PhD thesis entitled : 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 relevant concentrations of both drugs. We also investigated the effects of oxazolidinones on the differentiation process of platelets precursors.
Two papers have already been published :
- Milosevic TV, Payen VL, Sonveaux P, Muccioli GG, Tulkens PM, Van Bambeke F. Mitochondrial Alterations (Inhibition of Mitochondrial Protein Expression, Oxidative Metabolism, and Ultrastructure) Induced by Linezolid and Tedizolid at Clinically Relevant Concentrations in Cultured Human HL-60 Promyelocytes and THP-1 Monocytes. Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e01599-1
- Milosevic TV, Vertenoeil G, Payen VL, Sonveaux P, Tulkens PM, Constantinescu SN, Van Bambeke F. Prolonged inhibition and incomplete recovery of mitochondrial function in oxazolidinone-treated megakaryoblastic cell lines. Int J Antimicrob Agents. 2019 Jul 30. pii: S0924-8579(19)30210-9. doi: 10.1016/j.ijantimicag.2019.07.021