Using Caenorhabditis elegans for antimicrobial drug discovery

Expert Opinion on Drug Discovery

Volumn 6, Issue 6, 2011, Pages 645-652

  Desalermos, Athanasios ^a   Muhammed, Maged ^a   Glavis Bloom, Justin ^a   Mylonakis, Eleftherios ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Caenorhabditis elegans; Candida albicans; drug discovery; high throughput; model host

Indexed keywords

A16 AGINOSIDE; A2 SAKURASOSAPONIN; ABC TRANSPORTER; ANESTHETIC AGENT; ANTIBIOTIC AGENT; ANTIINFECTIVE AGENT; ANTINEOPLASTIC AGENT; ASCOMYCIN; CAFFEIC ACID PHENETHYL ESTER; CONCANAMYCIN A; CYCLOSPORIN A; CYTOCHROME P450; DEQUALINIUM; ENOXACIN; FLUCONAZOLE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KSI 4088; NEMADIPINE A; PHOSPHOLIPASE C; SAPONIN DERIVATIVE; TACROLIMUS; TREHALOSE; TRIADIMERON; UNCLASSIFIED DRUG;

ACINETOBACTER INFECTION; ALZHEIMER DISEASE; BIOFILM; CAENORHABDITIS ELEGANS; CANDIDA ALBICANS; CANDIDIASIS; CRYPTOCOCCUS NEOFORMANS; DRUG IDENTIFICATION; DRUG MECHANISM; DRUG RESEARCH; ENTEROCOCCUS FAECALIS; HEMOLYSIS; HIGH THROUGHPUT SCREENING; HOST; HOST PATHOGEN INTERACTION; HUMAN; IMMUNE SYSTEM; INNATE IMMUNITY; INOCULATION; MINIMUM INHIBITORY CONCENTRATION; MIXED INFECTION; MYCOSIS; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; RELIABILITY; REVIEW; SALMONELLA ENTERICA; SIGNAL TRANSDUCTION; STAPHYLOCOCCUS AUREUS; SURVIVAL; TOXICITY TESTING; VIRULENCE;

EID: 79957568547     PISSN: 17460441     EISSN: 1746045X     Source Type: Journal    
DOI: 10.1517/17460441.2011.573781     Document Type: Review

References (93)

1. Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974;6:71-94
2. Byerly L, Cassada RC, Russell RL. The life cycle of the nematode Caenorhabditis elegans. I. Wild-type growth and reproduction. Dev Biol 1976;51:23-33
3. Sulston JE, Brenner S. The DNA of Caenorhabditis elegans. Genetics 1974;77:95-104
4. C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 1998;282:2012-18
5. Jorgensen EM, Mango SE. The art and design of genetic screens: caenorhabditis elegans. Nat Rev Genet 2002;3:356-69 (Pubitemid 34506717)
6. Bieri T, Blasiar D, Ozersky P, et al. WormBase: new content and better access. Nucleic Acids Res 2007;35:D506-10
7. Chen N, Lawson D, Bradnam K, et al. WormBase as an integrated platform for the C. elegans ORFeome. Genome Res 2004;14:2155-61 (Pubitemid 39440198)
8. Harris TW, Antoshechkin I, Bieri T, et al. WormBase: a comprehensive resource for nematode research. Nucleic Acids Res 2010;38:D463-467
9. Rogers A, Antoshechkin I, Bieri T, et al. WormBase 2007. Nucleic Acids Res 2008;36:D612-17
10. Schwarz EM, Antoshechkin I, Bastiani C, et al. WormBase: better software, richer content. Nucleic Acids Res 2006;34:D475-8
11. Edmond MB, Wallace SE, McClish DK, et al. Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999;29:239-44 (Pubitemid 29380177)
12. Pfaller MA, Jones RN, Messer SA, et al. National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis 1998;31:327-32 (Pubitemid 28212061)
13. Miller LG, Hajjeh RA, Edwards JE Jr. Estimating the cost of nosocomial candidemia in the united states. Clin Infect Dis 2001;32:1110 (Pubitemid 32299650)
14. Rentz AM, Halpern MT, Bowden R. The impact of candidemia on length of hospital stay, outcome, and overall cost of illness. Clin Infect Dis 1998;27:781-8 (Pubitemid 29244335)
15. Walker LA, Gow NA, Munro CA. Fungal echinocandin resistance. Fungal Genet Biol 2010;47:117-26
16. Aperis G, Myriounis N, Spanakis EK, Mylonakis E. Developments in the treatment of candidiasis: more choices and new challenges. Expert Opin Investig Drugs 2006;15:1319-36 (Pubitemid 44615283)
17. Loeffler J, Stevens DA. Antifungal drug resistance. Clin Infect Dis 2003;36:S31-41
18. Pfaller MA, Lockhart SR, Pujol C, et al. Hospital specificity, region specificity, and fluconazole resistance of Candida albicans bloodstream isolates. J Clin Microbiol 1998;36:1518-29 (Pubitemid 28226023)
19. Antachopoulos C. Invasive fungal infections in congenital immunodeficiencies. Clin Microbiol Infect 2010;16:1335-42
20. Enwuru CA, Ogunledun A, Idika N, et al. Fluconazole resistant opportunistic oro-pharyngeal Candida and non-Candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria. Afr Health Sci 2008;8:142-8
21. Breger J, Fuchs BB, Aperis G, et al. Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog 2007;3:e18
22. Lo HJ, Kohler JR, DiDomenico B, et al. Nonfilamentous C. albicans mutants are avirulent. Cell 1997;90:939-49 (Pubitemid 27381632)
23. Saville SP, Lazzell AL, Bryant AP, et al. Inhibition of filamentation can be used to treat disseminated candidiasis. Antimicrob Agents Chemother 2006;50:3312-16 (Pubitemid 44527503)
24. Okoli I, Coleman JJ, Tampakakis E, et al. Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay. PLoS One 2009;4:e7025
25. Coleman JJ, Okoli I, Tegos GP, et al. Characterization of plant-derived saponin natural products against Candida albicans. ACS Chem Biol 2010;5:321-32
26. Means TK, Mylonakis E, Tampakakis E, et al. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med 2009;206:637-53
27. Boyd WA, McBride SJ, Rice JR, et al. A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay. Toxicol Appl Pharmacol 2010;245:153-9
28. Boyd WA, Smith MV, Kissling GE, Freedman JH. Medium- and high-throughput screening of neurotoxicants using C. elegans. Neurotoxicol Teratol 2010;32:68-73
29. Sochova I, Hofman J, Holoubek I. Using nematodes in soil ecotoxicology. Environ Int 2006;32:374-83 (Pubitemid 43328648)
30. Williams PL, Dusenbery DB. Using the nematode Caenorhabditis elegans to predict mammalian acute lethality to metallic salts. Toxicol Ind Health 1988;4:469-78 (Pubitemid 18268462)
31. Cole RD, Anderson GL, Williams PL. The nematode Caenorhabditis elegans as a model of organophosphate-induced mammalian neurotoxicity. Toxicol Appl Pharmacol 2004;194:248-56 (Pubitemid 38175287)
32. Cho BP, Yang T, Blankenship LR, et al. Synthesis and characterization of N-demethylated metabolites of malachite green and leucomalachite green. Chem Res Toxicol 2003;16:285-94 (Pubitemid 36373693)
33. Powell JR, Ausubel FM. Models of Caenorhabditis elegans infection by bacterial and fungal pathogens. Methods Mol Biol 2008;415:403-27
34. Sifri CD, Begun J, Ausubel FM. The worm has turned - microbial virulence modeled in Caenorhabditis elegans. Trends Microbiol 2005;13:119-27 (Pubitemid 40311894)
35. Moy TI, Ball AR, Anklesaria Z, et al. Identification of novel antimicrobials using a live-animal infection model. Proc Natl Acad Sci USA 2006;103:10414-19 (Pubitemid 44051181)
36. Moy TI, Conery AL, Larkins-Ford J, et al. High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem Biol 2009;4:527-33
37. Kaewintajuk K, Cho PY, Kim SY, et al. Anthelmintic activity of KSI-4088 against Caenorhabditis elegans. Parasitol Res 2010;107:27-30
38. Aballay A, Ausubel FM. Caenorhabditis elegans as a host for the study of host-pathogen interactions. Curr Opin Microbiol 2002;5:97-101 (Pubitemid 34118165)
39. Fuchs BB, Mylonakis E. Using non-mammalian hosts to study fungal virulence and host defense. Curr Opin Microbiol 2006;9:346-51 (Pubitemid 44108716)
40. Irazoqui JE, Ausubel FM. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Caenorhabditis elegans as a model to study tissues involved in host immunity and microbial pathogenesis. Clin Exp Immunol 2010;160:48-57
41. Irazoqui JE, Ng A, Xavier RJ, Ausubel FM. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions. Proc Natl Acad Sci USA 2008;105:17469-74
42. Irazoqui JE, Urbach JM, Ausubel FM. Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 2010;10:47-58
43. Miyata S, Begun J, Troemel ER, Ausubel FM. DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans. Genetics 2008;178:903-18 (Pubitemid 351398801)
44. Mylonakis E, Aballay A. Worms and flies as genetically tractable animal models to study host-pathogen interactions. Infect Immun 2005;73:3833-41 (Pubitemid 40923120)
45. Mylonakis E, Ausubel FM, Perfect JR, et al. Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis. Proc Natl Acad Sci USA 2002;99:15675-80 (Pubitemid 35403990)
46. Mylonakis E, Ausubel FM, Tang RJ, Calderwood SB. The art of serendipity: killing of Caenorhabditis elegans by human pathogens as a model of bacterial and fungal pathogenesis. Expert Rev Anti Infect Ther 2003;1:167-73 (Pubitemid 38735737)
47. Mylonakis E, Casadevall A, Ausubel FM. Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi. PLoS Pathog 2007;3:e101
48. Mylonakis E, Idnurm A, Moreno R, et al. Cryptococcus neoformans Kin1 protein kinase homologue, identified through a Caenorhabditis elegans screen, promotes virulence in mammals. Mol Microbiol 2004;54:407-19 (Pubitemid 39388285)
49. Pukkila-Worley R, Peleg AY, Tampakakis E, Mylonakis E. Candida albicans hyphal formation and virulence assessed using a Caenorhabditis elegans infection model. Eukaryot Cell 2009;8:1750-8
50. Tang RJ, Breger J, Idnurm A, et al. Cryptococcus neoformans gene involved in mammalian pathogenesis identified by a Caenorhabditis elegans progeny-based approach. Infect Immun 2005;73:8219-25 (Pubitemid 41740311)
51. Elbein AD. The metabolism of alpha,alpha-trehalose. Adv Carbohydr Chem Biochem 1974;30:227-56
52. Wiemken A. Trehalose in yeast, stress protectant rather than reserve carbohydrate. Antonie Van Leeuwenhoek 1990;58:209-17 (Pubitemid 20302573)
53. Himmelreich U, Allen C, Dowd S, et al. Identification of metabolites of importance in the pathogenesis of pulmonary cryptococcoma using nuclear magnetic resonance spectroscopy. Microbes Infect 2003;5:285-90 (Pubitemid 36428717)
54. Petzold EW, Himmelreich U, Mylonakis E, et al. Characterization and regulation of the trehalose synthesis pathway and its importance in the pathogenicity of Cryptococcus neoformans. Infect Immun 2006;74:5877-87 (Pubitemid 44484575)
55. Chayakulkeeree M, Sorrell TC, Siafakas AR, et al. Role and mechanism of phosphatidylinositol-specific phospholipase C in survival and virulence of Cryptococcus neoformans. Mol Microbiol 2008;69:809-26 (Pubitemid 352033304)
56. Cox GM, McDade HC, Chen SC, et al. Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans. Mol Microbiol 2001;39:166-75 (Pubitemid 32057686)
57. Ganendren R, Carter E, Sorrell T, et al. Phospholipase B activity enhances adhesion of Cryptococcus neoformans to a human lung epithelial cell line. Microbes Infect 2006;8:1006-15
58. Santangelo R, Zoellner H, Sorrell T, et al. Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model. Infect Immun 2004;72:2229-39 (Pubitemid 38419938)
59. Siafakas AR, Sorrell TC, Wright LC, et al. Cell wall-linked cryptococcal phospholipase B1 is a source of secreted enzyme and a determinant of cell wall integrity. J Biol Chem 2007;282:37508-14
60. Peleg AY, Tampakakis E, Fuchs BB, et al. Prokaryote-eukaryote interactions identified by using Caenorhabditis elegans. Proc Natl Acad Sci USA 2008;105:14585-90
61. Liu CH, Chen X, Liu TT, et al. Study of the antifungal activity of Acinetobacter baumannii LCH001 in vitro and identification of its antifungal components. Appl Microbiol Biotechnol 2007;76:459-66 (Pubitemid 47101675)
62. Chim H, Tan BH, Song C. Five-year review of infections in a burn intensive care unit: high incidence of Acinetobacter baumannii in a tropical climate. Burns 2007;33:1008-14 (Pubitemid 350051191)
63. Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev 2008;21:538-82
64. Artal-Sanz M, de Jong L, Tavernarakis N. Caenorhabditis elegans: a versatile platform for drug discovery. Biotechnol J 2006;1:1405-18
65. Burns AR, Kwok TC, Howard A, et al. High-throughput screening of small molecules for bioactivity and target identification in Caenorhabditis elegans. Nat Protoc 2006;1:1906-14 (Pubitemid 46773310)
66. Kwok TC, Ricker N, Fraser R, et al. A small-molecule screen in C. elegans yields a new calcium channel antagonist. Nature 2006;441:91-5
67. Pukkila-Worley R, Holson E, Wagner F, Mylonakis E. Antifungal drug discovery through the study of invertebrate model hosts. Curr Med Chem 2009;16:1588-95
68. Segalat L. Drug discovery: here comes the worm. ACS Chem Biol 2006;1:277-8
69. Tampakakis E, Okoli I, Mylonakis E. A C. elegans-based, whole animal, in vivo screen for the identification of antifungal compounds. Nat Protoc 2008;3:1925-31
70. Steele LM, Sedensky MM, Morgan PG. Alternatives to mammalian pain models 1: use of C. elegans for the study of volatile anesthetics. Methods Mol Biol 2010;617:1-17
71. Kimura Y, Corcoran EE, Eto K, et al. A CaMK cascade activates CRE-mediated transcription in neurons of Caenorhabditis elegans. EMBO Rep 2002;3:962-6 (Pubitemid 35256470)
72. Zubenko GS, Jones ML, Estevez AO, et al. Identification of a CREB-dependent serotonergic pathway and neuronal circuit regulating foraging behavior in Caenorhabditis elegans: a useful model for mental disorders and their treatments? Am J Med Genet B Neuropsychiatr Genet 2009;150B:12-23
73. Jospin M, Jacquemond V, Mariol MC, et al. The L-type voltage-dependent Ca2+ channel EGL-19 controls body wall muscle function in Caenorhabditis elegans. J Cell Biol 2002;159:337-48
74. Lee RY, Lobel L, Hengartner M, et al. Mutations in the alpha1 subunit of an L-type voltage-activated Ca2+ channel cause myotonia in Caenorhabditis elegans. Embo J 1997;16:6066-76 (Pubitemid 27458326)
75. Deng X, Hofmann ER, Villanueva A, et al. Caenorhabditis elegans ABL-1 antagonizes p53-mediated germline apoptosis after ionizing irradiation. Nat Genet 2004;36:906-12 (Pubitemid 39014112)
76. Carre-Pierrat M, Mariol MC, Chambonnier L, et al. Blocking of striated muscle degeneration by serotonin in C. elegans. J Muscle Res Cell Motil 2006;27:253-8 (Pubitemid 43999253)
77. Link CD. C. elegans models of age-associated neurodegenerative diseases: lessons from transgenic worm models of Alzheimer's disease. Exp Gerontol 2006;41:1007-13 (Pubitemid 44821699)
78. Morcos M, Hutter H. The model Caenorhabditis elegans in diabetes mellitus and Alzheimer's disease. J Alzheimers Dis 2009;16:897-908
79. Schlotterer A, Kukudov G, Bozorgmehr F, et al. C. elegans as model for the study of high glucose- mediated life span reduction. Diabetes 2009;58:2450-6
80. Smialowska A, Baumeister R. Presenilin function in Caenorhabditis elegans. Neurodegener Dis 2006;3:227-32 (Pubitemid 44600308)
81. Kaletta T, Hengartner MO. Finding function in novel targets: C. elegans as a model organism. Nat Rev Drug Discov 2006;5:387-98
82. Macarron R, Hertzberg RP. Design and implementation of high throughput screening assays. Mol Biotechnol 2011;47:270-85
83. Macarron R, Hertzberg RP. Design and implementation of high throughput screening assays. Methods Mol Biol 2002;190:1-29
84. Macarron R, Hertzberg RP. Design and implementation of high-throughput screening assays. Methods Mol Biol 2009;565:1-32
85. O'Rourke EJ, Conery AL, Moy TI. Whole-animal high-throughput screens: the C. elegans model. Methods Mol Biol 2009;486:57-75
86. Segalat L. Invertebrate animal models of diseases as screening tools in drug discovery. ACS Chem Biol 2007;2:231-6 (Pubitemid 47629209)
87. Coleman JJ, Mylonakis E. The tangled web of signaling in innate immunity. Cell Host Microbe 2009;5:313-15
88. Ziegler K, Kurz CL, Cypowyj S, et al. Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade. Cell Host Microbe 2009;5:341-52
89. Ren M, Feng H, Fu Y, et al. Protein kinase D is an essential regulator of C. elegans innate immunity. Immunity 2009;30:521-32
90. Cox GN, Kusch M, Edgar RS. Cuticle of Caenorhabditis elegans: its isolation and partial characterization. J Cell Biol 1981;90:7-17
91. Avery L, Shtonda BB. Food transport in the C. elegans pharynx. J Exp Biol 2003;206:2441-57 (Pubitemid 36914464)
92. Burns AR, Wallace IM, Wildenhain J, et al. A predictive model for drug bioaccumulation and bioactivity in Caenorhabditis elegans. Nat Chem Biol 2010;6:549-57
93. Gosai SJ, Kwak JH, Luke CJ, et al. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin alpha1-antitrypsin Z. PLoS One 2010;5:e15460