Cytoskeleton reassembly in cardiomyocytes infected by Trypanosoma cruzi is triggered by treatment with ergosterol biosynthesis inhibitors

• Published in: International journal of antimicrobial agents Vol. 27; no. 6; pp. 530 - 537
• Main Authors: Silva, Dayse T., de Meirelles, Maria de Nazareth S.L., Almeida, Danielle, Urbina, Julio A., Pereira, Mirian Claudia S.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 01.06.2006; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cardiomyocytes; Cells, Cultured; Cytoskeleton; Cytoskeleton - chemistry; Cytoskeleton - drug effects; Ergosterol - antagonists & inhibitors; Ergosterol - biosynthesis; Ergosterol biosynthesis inhibitors; Ketoconazole - pharmacology; Medical sciences; Mice; Myocytes, Cardiac - chemistry; Myocytes, Cardiac - drug effects; Myofibrils - drug effects; Pharmacology. Drug treatments; Triazoles - pharmacology; Trypanocidal Agents - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Cardiomyocytes; Cytoskeleton; Ergosterol biosynthesis inhibitors; Trypanosoma cruzi; Kinetoplastida; Infection; Protozoa; Ergosterol; Treatment; Biosynthesis; Inhibitor
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2005.12.012

We have previously shown that Trypanosoma cruzi-infected cardiomyocytes present alterations in cytoskeletal organisation in vitro. The remarkable change in the host cell cytoskeleton opened up the question of whether treatment of infected cells with antitrypanosomal compounds, such as ergosterol biosynthesis inhibitors (EBIs), allows the reconstruction of myofibrils and the microtubule network, restoring the cell biological function. Therefore, 48-h-old T. cruzi-infected cardiomyocyte cultures were treated with 10 nM ketoconazole or posaconazole and cytoskeletal remodelling of the host cells was analysed by indirect immunofluorescence assay. Both compounds displayed a potent antiparasitic effect and dramatically reduced the infection ratio. After 120 h of treatment, actin polygonal configuration was frequently visualised in the host cell cytoplasm, suggesting the initial stage of actin framework restoration. Rearrangement of myofibrils and the microtubule network was achieved 168 h after the start of drug treatment. Our data demonstrate that the trypanocidal effect of EBIs lead to reconstruction of the cytoskeleton of T. cruzi-infected cardiomyocytes in vitro.