Exploring the inhibitory potential of the antiarrhythmic drug amiodarone against Clostridioides difficile toxins TcdA and TcdB

References

• Kelly CP, LaMont JT. Clostridium difficile — more difficult than ever. N Engl J Med. 2008;359(18):1932–19. doi:10.1056/NEJMra0707500.
   PubMed Web of Science ®Google Scholar
• Aktories K, Schwan C, Jank T. Clostridium difficile toxin biology. Annu Rev Microbiol. 2017;71(1):281–307. doi:10.1146/annurev-micro-090816-093458.
   PubMed Web of Science ®Google Scholar
• Chandrasekaran R, Lacy DB. The role of toxins in Clostridium difficile infection. FEMS Microbiol Rev. 2017;41(6):723–750. doi:10.1093/femsre/fux048.
   PubMed Web of Science ®Google Scholar
• Just I, Selzer J, Wilm M, Eichel-Streiber CV, Mann M, Aktories K. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature. 1995;375:500–503. doi:10.1038/375500a0.
   PubMed Web of Science ®Google Scholar
• H A. Small GTP-binding proteins and the regulation of the actin cytoskeleton. Annu Rev Cell Biol. 1994;10(1):31–54. doi:10.1146/annurev.cb.10.110194.000335.
   PubMedGoogle Scholar
• Aktories K, Just I. Clostridial Rho-inhibiting protein toxins. Curr Top Microbiol Immunol. 2005;291:113–145.
   PubMed Web of Science ®Google Scholar
• Papatheodorou P, Zamboglou C, Genisyuerek S, Guttenberg G, Aktories K. Clostridial glucosylating toxins enter cells via clathrin-mediated endocytosis. PloS One. 2010;5(5):e10673. doi:10.1371/journal.pone.0010673.
   PubMed Web of Science ®Google Scholar
• Gerhard R, Frenzel E, Goy S, Olling A. Cellular uptake of Clostridium difficile TcdA and truncated TcdA lacking the receptor binding domain. J Med Microbiol. 2013;62(9):1414–1422. doi:10.1099/jmm.0.057828-0.
   PubMedGoogle Scholar
• Chandrasekaran R, Kenworthy AK, Lacy DB. Clostridium difficile toxin a undergoes clathrin-independent, PACSIN2-dependent endocytosis. PLoS Pathog. 2016;12(12):12. doi:10.1371/journal.ppat.1006070.
   Web of Science ®Google Scholar
• Gerhard R. Receptors and binding structures for Clostridium difficile toxins A and B. Curr Top Microbiol Immunol. 2017;406:79–96.
   PubMed Web of Science ®Google Scholar
• Papatheodorou P, Barth H, Minton N, Aktories K. Cellular uptake and mode-of-action of Clostridium difficile toxins. Adv Exp Med Biol. 2018;1050:77–96.
   PubMed Web of Science ®Google Scholar
• Barth H, Pfeifer G, Hofmann F, Maier E, Benz R, Aktories K. Low pH-induced formation of ion channels by Clostridium difficile toxin B in target cells. J Biol Chem. 2001;276(14):10670–10676. doi:10.1074/jbc.M009445200.
   PubMed Web of Science ®Google Scholar
• Orrell KE, Zhang Z, Sugiman-Marangos SN, Melnyk RA. Clostridium difficile toxins A and B: receptors, pores, and translocation into cells. Crit Rev Biochem Mol Biol. 2017;52(4):461–473. doi:10.1080/10409238.2017.1325831.
   PubMed Web of Science ®Google Scholar
• Jank T, Aktories K. Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol. 2008;16(5):222–229. doi:10.1016/j.tim.2008.01.011.
   PubMed Web of Science ®Google Scholar
• Giesemann T, Egerer M, Jank T, Aktories K. Processing of Clostridium difficile toxins. J Med Microbiol. 2008;57(6):690–696. doi:10.1099/jmm.0.47742-0.
   PubMed Web of Science ®Google Scholar
• Egerer M, Giesemann T, Herrmann C, Aktories K. Autocatalytic processing of Clostridium difficile toxin B: binding of inositol hexakisphosphate. J Biol Chem. 2009;284:3389–3395. doi:10.1074/jbc.M806002200.
   PubMed Web of Science ®Google Scholar
• Giesemann T, Jank T, Gerhard R, Maier E, Just I, Benz R, Aktories K. Cholesterol-dependent pore formation of Clostridium difficile toxin A. J Biol Chem. 2006;281(16):10808–10815. doi:10.1074/jbc.M512720200.
   PubMed Web of Science ®Google Scholar
• Papatheodorou P, Song S, López-Ureña D, Witte A, Marques F, Ost GS, Schorch B, Chaves-Olarte E, Aktories K. Cytotoxicity of Clostridium difficile toxins A and B requires an active and functional SREBP-2 pathway. FASEB J. 2019;33(4):4883–4892. doi:10.1096/fj.201801440R.
   PubMed Web of Science ®Google Scholar
• Papatheodorou P, Kindig S, Badilla-Lobo A, Fischer S, Durgun E, Thuraisingam T, Witte A, Song S, Aktories K, Chaves-Olarte E, et al. The compound U18666A inhibits the intoxication of cells by Clostridioides difficile toxins TcdA and TcdB. Front Microbiol. 2021;12:12. doi:10.3389/fmicb.2021.784856.
   Web of Science ®Google Scholar
• Kodama I, Kamiya K, Toyama J. Cellular electropharmacology of amiodarone. Cardiovasc Res. 1997;35:13–29. doi:10.1016/S0008-6363(97)00114-4.
   PubMed Web of Science ®Google Scholar
• Simonen P, Li S, Chua NK, Lampi AM, Piironen V, Lommi J, Sinisalo J, Brown AJ, Ikonen E, Gylling H. Amiodarone disrupts cholesterol biosynthesis pathway and causes accumulation of circulating desmosterol by inhibiting 24-dehydrocholesterol reductase. J Intern Med. 2020;288(5):560–569. doi:10.1111/joim.13095.
   PubMed Web of Science ®Google Scholar
• Allen LB, Genaro-Mattos TC, Anderson A, Porter NA, Mirnics K, Korade Z. Amiodarone alters cholesterol biosynthesis through tissue-dependent inhibition of Emopamil binding protein and dehydrocholesterol reductase 24. ACS Chem Neurosci. 2020;11(10):1413–1423. doi:10.1021/acschemneuro.0c00042.
   PubMed Web of Science ®Google Scholar
• Barsi S, Papp H, Valdeolivas A, Tóth DJ, Kuczmog A, Madai M, Hunyady L, Várnai P, Saez-Rodriguez J, Jakab F, et al. Computational drug repurposing against SARS-CoV-2 reveals plasma membrane cholesterol depletion as key factor of antiviral drug activity. PLoS Comput Biol. 2022;18(4):18. doi:10.1371/journal.pcbi.1010021.
   Web of Science ®Google Scholar
• Heber S, Barthold L, Baier J, Papatheodorou P, Fois G, Frick M, Barth H, Fischer S. Inhibition of Clostridioides difficile toxins TcdA and TcdB by Ambroxol. Front Pharmacol. 2022;12:12. doi:10.3389/fphar.2021.809595.
   Web of Science ®Google Scholar
• Wu K-H, Tai PC. Cys32 and His105 are the critical residues for the calcium-dependent cysteine proteolytic activity of CvaB, an ATP-binding cassette transporter. J Biol Chem. 2004;279(2):901–909. doi:10.1074/jbc.M308296200.
   PubMed Web of Science ®Google Scholar
• Salas Rojas M, Silva Garcia R, Bini E, Pérez de la Cruz V, León Contreras JC, Hernández Pando R, Bastida Gonzalez F, Davila-Gonzalez E, Orozco Morales M, Gamboa Domínguez A, et al. Quinacrine, an antimalarial drug with strong activity inhibiting SARS-CoV-2 viral replication in vitro. Viruses. 2021;13:121. doi:10.3390/v13010121.
   PubMed Web of Science ®Google Scholar
• Sanchez AM, Thomas D, Gillespie EJ, Damoiseaux R, Rogers J, Saxe JP, Huang J, Manchester M, Bradley KA. Amiodarone and bepridil inhibit anthrax toxin entry into host cells. Antimicrob Agents Chemother. 2007;51(7):2403–2411. doi:10.1128/AAC.01184-06.
   PubMed Web of Science ®Google Scholar
• Piccoli E, Nadai M, Caretta CM, Bergonzini V, Del Vecchio C, Ha HR, Bigler L, Dal Zoppo D, Faggin E, Pettenazzo A, et al. Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C-like phenotype. Biochem Pharmacol. 2011;82(9):1234–1249. doi:10.1016/j.bcp.2011.07.090.
   PubMed Web of Science ®Google Scholar
• Lord JM, Roberts LM. Retrograde transport: going against the flow. Curr Biol. 1998;8(2):R56–8. doi:10.1016/S0960-9822(98)70034-X.
   PubMed Web of Science ®Google Scholar
• Singh BN, Vaughan Williams EM. The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmac. 1970;39:657–667. doi:10.1111/j.1476-5381.1970.tb09891.x.
   PubMed Web of Science ®Google Scholar
• Nattel S, Singh BN. Evolution, mechanisms, and classification of antiarrhythmic drugs: focus on class III actions. Am J Cardiol. 1999;84(9):11–19. doi:10.1016/S0002-9149(99)00697-9.
   Google Scholar
• Wu L, Rajamani S, Shryock JC, Li H, Ruskin J, Antzelevitch C, Belardinelli L. Augmentation of late sodium current unmasks the proarrhythmic effects of amiodarone. Cardiovasc Res. 2008;77:481–488. doi:10.1093/cvr/cvm069.
   PubMed Web of Science ®Google Scholar
• Ghovanloo MR, Abdelsayed M, Ruben PC. Effects of amiodarone and N-desethylamiodarone on cardiac voltage-gated sodium channels. Front Pharmacol. 2016;7. doi:10.3389/fphar.2016.00039.
   PubMed Web of Science ®Google Scholar
• Genisyuerek S, Papatheodorou P, Guttenberg G, Schubert R, Benz R, Aktories K. Structural determinants for membrane insertion, pore formation and translocation of Clostridium difficile toxin B. Mol Microbiol. 2011;79(6):1643–1654. doi:10.1111/j.1365-2958.2011.07549.x.
   PubMed Web of Science ®Google Scholar
• Marozsan AJ, Ma D, Nagashima KA, Kennedy BJ, Kang YK, Arrigale RR, Donovan GP, Magargal WW, Maddon PJ, Olson WC. Protection against Clostridium difficile infection with broadly neutralizing antitoxin monoclonal antibodies. J Infect Dis. 2012;206:706–713. doi:10.1093/infdis/jis416.
   PubMed Web of Science ®Google Scholar
• Hernandez LD, Racine F, Xiao L, DiNunzio E, Hairston N, Sheth PR, Murgolo NJ, Therien AG. Broad coverage of genetically diverse strains of Clostridium difficile by actoxumab and bezlotoxumab predicted by in vitro neutralization and epitope modeling. Antimicrob Agents Chemother. 2015;59(2):1052. doi:10.1128/AAC.04433-14.
   PubMed Web of Science ®Google Scholar
• Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet. 1984;9(2):136–156. doi:10.2165/00003088-198409020-00002.
   PubMed Web of Science ®Google Scholar
• Raeder EA, Podrid PJ, Lown B. Side effects and complications of amiodarone therapy. Am Heart J. 1985;109(5):975–983. doi:10.1016/0002-8703(85)90238-8.
   PubMed Web of Science ®Google Scholar
• Goldschlager N, Epstein AE, Naccarelli GV, Olshansky B, Singh B, Collard HR, Murphy E. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm. 2007;4:1250–1259. doi:10.1016/j.hrthm.2007.07.020.
   PubMed Web of Science ®Google Scholar
• Barra S, Primo J, Gonçalves H, Boveda S, Providência R, Grace A. Is amiodarone still a reasonable therapeutic option for rhythm control in atrial fibrillation? Rev Port Cardiol. 2022;41:783–789. doi:10.1016/j.repc.2021.03.019.
   PubMedGoogle Scholar
• Yalta K, Turgut OO, Yilmaz MB, Yilmaz A, Tandogan I. Dronedarone: a promising alternative for the management of atrial fibrillation. Cardiovasc Drugs Ther. 2009;23:385–393. doi:10.1007/s10557-009-6189-0.
   PubMed Web of Science ®Google Scholar
• Khan MH, Rochlani Y, Aronow WS. Efficacy and safety of dronedarone in the treatment of patients with atrial fibrillation. Expert Opin Drug Saf. 2017;16(12):1407–1412. doi:10.1080/14740338.2017.1387246.
   PubMed Web of Science ®Google Scholar
• Hohwieler M, Renz S, Liebau S, Lin Q, Lechel A, Klaus J, Perkhofer L, Zenke M, Seufferlein T, Illing A, et al. “Miniguts” from plucked human hair meet Crohn’s disease. Z Gastroenterol. 2016;54(8):748–759. doi:10.1055/s-0042-105520.
   PubMed Web of Science ®Google Scholar
• Hohwieler M, Illing A, Hermann PC, Mayer T, Stockmann M, Perkhofer L, Eiseler T, Antony JS, Müller M, Renz S, et al. Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut. 2017;66(3):473–486. doi:10.1136/gutjnl-2016-312423.
   PubMed Web of Science ®Google Scholar
• Ernst K, Schmid J, Beck M, Hägele M, Hohwieler M, Hauff P, Ückert AK, Anastasia A, Fauler M, Jank T, et al. Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells. Sci Rep. 2017;7(1). doi:10.1038/s41598-017-02882-y.
   Google Scholar
• Zhu Z, Schnell L, Müller B, Müller M, Papatheodorou P, Barth H. The antibiotic bacitracin protects human intestinal epithelial cells and stem cell-derived intestinal organoids from Clostridium difficile toxin TcdB. Stem Cells Int. 2019;2019:1–8. doi:10.1155/2019/4149762.
   Web of Science ®Google Scholar
• Lyerly DM, Krivan HC, Wilkins TD. Clostridium difficile: its disease and toxins. Clin Microbiol Rev. 1988;1(1):1–18. doi:10.1128/CMR.1.1.1.
   PubMedGoogle Scholar
• Pruitt RN, Chambers MG, Ng KKS, Ohi MD, Lacy DB. Structural organization of the functional domains of Clostridium difficile toxins A and B. Proc Natl Acad Sci USA. 2010;107(30):13467–13472. doi:10.1073/pnas.1002199107.
   PubMed Web of Science ®Google Scholar
• Just I, Selzer J, Hofmann F, Aktories K. Clostridium difficile toxin B as a probe for Rho GTPases. In: Aktories K, editor. Bact Toxins. 1997. doi:10.1002/9783527614615.ch13.
   Google Scholar