Genetic evidence for cytochrome b Qi site inhibition by 4(1H)-quinolone-3-diarylethers and antimycin in Toxoplasma gondii

Antimicrobial Agents and Chemotherapy

Volumn 61, Issue 2, 2017, Pages

  Alday, P Holland ^a   Bruzual, Igor ^b   Nilsen, Aaron ^b   Pou, Sovitj ^b   Winter, Rolf ^b   Mamoun, Choukri Ben ^c   Riscoe, Michael K ^b   Doggett, J Stone ^a,b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b PORTLAND VA MEDICAL CENTER   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apicomplexan parasites; Cytochrome b; Cytochrome bc1; Drug targets; Experimental therapeutics; Mechanisms of action; Mitochondria; Parasitology; Preclinical drug studies; Toxoplasma gondii

Indexed keywords

4(1H) QUINOLONE 3 DIARYLETHER DERIVATIVE; ANTIMYCIN A1; ATOVAQUONE; CITRININ; CYTOCHROME B; CYTOCHROME B Q I; ENDOCHINLIKE QUINOLONE 271; ENDOCHINLIKE QUINOLONE 316; QUINOLONE DERIVATIVE; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; GENE MUTATION; HUMAN; HUMAN CELL; NONHUMAN; NUCLEOTIDE SEQUENCE; PHYLOGENY; PRIORITY JOURNAL; TOXOPLASMA GONDII; ANALOGS AND DERIVATIVES; DRUG EFFECTS; GENETICS; METABOLISM; MITOCHONDRION; PARASITOLOGY; TOXOPLASMA; TOXOPLASMOSIS;

ANTIMYCIN A; CYTOCHROMES B; MITOCHONDRIA; QUINOLONES; TOXOPLASMA; TOXOPLASMOSIS;

EID: 85010934737     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01866-16     Document Type: Article

References (29)

1. Tenter AM, Heckeroth AR, Weiss LM. 2000. Toxoplasma gondii: from animals to humans. Int J Parasitol 30:1217-1258. https://doi.org/10.1016/S0020-7519(00)00124-7.
2. Grigg ME, Dubey JP, Nussenblatt RB. 2015. Ocular toxoplasmosis: lessons from Brazil. Am J Ophthalmol 159:999-1001. https://doi.org/10.1016/j.ajo.2015.04.005.
3. Yan J, Huang B, Liu G, Wu B, Huang S, Zheng H, Shen J, Lun ZR, Wang Y, Lu F. 2013. Meta-analysis of prevention and treatment of toxoplasmic encephalitis in HIV-infected patients. Acta Trop 127:236-244. https://doi.org/10.1016/j.actatropica.2013.05.006.
4. Chirgwin K, Hafner R, Leport C, Remington J, Andersen J, Bosler EM, Roque C, Rajicic N, McAuliffe V, Morlat P, Jayaweera DT, Vilde JL, Luft BJ. 2002. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. Clin Infect Dis 34:1243-1250. https://doi.org/10.1086/339551.
5. Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, Toovey S, Knobloch J, Nothdurft HD, Shaw D, Roskell NS, Chulay JD, Malarone International Study Team. 2001. Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study. Clin Infect Dis 33:1015-1021. https://doi.org/10.1086/322694.
6. Bergdoll L, Ten Brink F, Nitschke W, Picot D, Baymann F. 2016. From low-to high-potential bioenergetic chains: thermodynamic constraints of Q-cycle function. Biochim Biophys Acta 1857:1569-1579. https://doi.org/10.1016/j.bbabio.2016.06.006.
7. Vannier E, Krause PJ. 2012. Human babesiosis. N Engl J Med 366:2397-2407. https://doi.org/10.1056/NEJMra1202018.
8. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. 2016. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult-oi.pdf. Accessed 17 July 2016.
9. Potter VR, Reif AE. 1952. Inhibition of an electron transport component by antimycin A. J Biol Chem 194:287-297.
10. Capper MJ, O'Neill PM, Fisher N, Strange RW, Moss D, Ward SA, Berry NG, Lawrenson AS, Hasnain SS, Biagini GA, Antonyuk SV. 2015. Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1. Proc Natl Acad Sci U S A 112:755-760. https://doi.org/10.1073/pnas.1416611112.
11. Nilsen A, Miley GP, Forquer IP, Mather MW, Katneni K, Li Y, Pou S, Pershing AM, Stickles AM, Ryan E, Kelly JX, Doggett JS, White KL, Hinrichs DJ, Winter RW, Charman SA, Zakharov LN, Bathurst I, Burrows JN, Vaidya AB, Riscoe MK. 2014. Discovery, synthesis, and optimization of antimalarial 4(1H)-quinolone-3-diarylethers. J Med Chem 57:3818-3834. https://doi.org/10.1021/jm500147k.
12. Doggett JS, Nilsen A, Forquer I, Wegmann KW, Jones-Brando L, Yolken RH, Bordon C, Charman SA, Katneni K, Schultz T, Burrows JN, Hinrichs DJ, Meunier B, Carruthers VB, Riscoe MK. 2012. Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis. Proc Natl Acad Sci U S A 109:15936-15941. https://doi.org/10.1073/pnas.1208069109.
13. Lawres LA, Garg A, Kumar V, Bruzual I, Forquer IP, Renard I, Virji AZ, Boulard P, Rodriguez EX, Allen AJ, Pou S, Wegmann KW, Winter RW, Nilsen A, Mao J, Preston DA, Belperron AA, Bockenstedt LK, Hinrichs DJ, Riscoe MK, Doggett JS, Ben Mamoun C. 2016. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone. J Exp Med 213:1307-1318. https://doi.org/10.1084/jem.20151519.
14. Stickles AM, de Almeida MJ, Morrisey JM, Sheridan KA, Forquer IP, Nilsen A, Winter RW, Burrows JN, Fidock DA, Vaidya AB, Riscoe MK. 2015. Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum. Antimicrob Agents Chemother 59:1977-1982. https://doi.org/10.1128/AAC.04149-14.
15. Hegewald J, Gross U, Bohne W. 2013. Identification of dihydroorotate dehydrogenase as a relevant drug target for 1-hydroxyquinolones in Toxoplasma gondii. Mol Biochem Parasitol 190:6-15. https://doi.org/10.1016/j.molbiopara.2013.05.008.
16. Vallieres C, Fisher N, Antoine T, Al-Helal M, Stocks P, Berry NG, Lawrenson AS, Ward SA, O'Neill PM, Biagini GA, Meunier B. 2012. HDQ, a potent inhibitor of Plasmodium falciparum proliferation, binds to the quinone reduction site of the cytochrome bc1 complex. Antimicrob Agents Chemother 56:3739-3747. https://doi.org/10.1128/AAC.00486-12.
17. McFadden DC, Tomavo S, Berry EA, Boothroyd JC. 2000. Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance. Mol Biochem Parasitol 108:1-12. https://doi.org/10.1016/S0166-6851(00)00184-5.
18. Gjerde B. 2013. Characterisation of full-length mitochondrial copies and partial nuclear copies (numts) of the cytochrome b and cytochrome c oxidase subunit I genes of Toxoplasma gondii, Neospora caninum, Hammondia heydorni and Hammondia triffittae (Apicomplexa: Sarcocystidae). Parasitol Res 112:1493-1511. https://doi.org/10.1007/s00436-013-3296-4.
19. Huang LS, Cobessi D, Tung EY, Berry EA. 2005. Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc1 complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern. J Mol Biol 351:573-597. https://doi.org/10.1016/j.jmb.2005.05.053.
20. Hunte C, Palsdottir H, Trumpower BL. 2003. Protonmotive pathways and mechanisms in the cytochrome bc1 complex. FEBS Lett 545:39-46. https://doi.org/10.1016/S0014-5793(03)00391-0.
21. Gao X, Wen X, Esser L, Quinn B, Yu L, Yu CA, Xia D. 2003. Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site. Biochemistry 42:9067-9080. https://doi.org/10.1021/bi0341814.
22. Lange C, Hunte C. 2002. Crystal structure of the yeast cytochrome bc1 complex with its bound substrate cytochrome c. Proc Natl Acad Sci U S A 99:2800-2805. https://doi.org/10.1073/pnas.052704699.
23. Coleman BI, Gubbels MJ. 2012. A genetic screen to isolate Toxoplasma gondii host-cell egress mutants. J Vis Exp 2012:e3807. https://doi.org/10.3791/3807.
24. Guzman C, Bagga M, Kaur A, Westermarck J, Abankwa D. 2014. ColonyArea: an ImageJ plugin to automatically quantify colony formation in clonogenic assays. PLoS One 9:e92444. https://doi.org/10.1371/journal.pone.0092444.
25. Edgar RC. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792-1797. https://doi.org/10.1093/nar/gkh340.
26. Boratyn GM, Schaffer AA, Agarwala R, Altschul SF, Lipman DJ, Madden TL. 2012. Domain enhanced lookup time accelerated BLAST. Biol Direct 7:12. https://doi.org/10.1186/1745-6150-7-12.
27. Whelan S, Goldman N. 2001. A general empirical model of protein evolution derived from multiple protein families using a maximum-likelihood approach. Mol Biol Evol 18:691-699. https://doi.org/10.1093/oxfordjournals.molbev.a003851.
28. Felsenstein J. 1985. Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783-791. https://doi.org/10.2307/2408678.
29. Kumar S, Stecher G, Tamura K. 2016. MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870-1874. https://doi.org/10.1093/molbev/msw054.