A potent plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 6, 2012, Pages 2894-2907

  Xu, Tao ^a,e   Tripathi, Siddharth K ^a   Feng, Qin ^a   Lorenz, Michael C ^b   Wright, Marsha A ^a   Jacob, Melissa R ^a   Mask, Melanie M ^c   Baerson, Scott R ^c   Li, Xing Cong ^a   Clark, Alice M ^a,d   Agarwala, Ameeta K ^a  

^a UNIVERSITY OF MISSISSIPPI   (United States)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^c NATURAL PRODUCTS UTILIZATION RESEARCH UNIT   (United States)

^d UNIVERSITY OF MISSISSIPPI   (United States)

^e UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 NONADECYNOIC ACID; ANTIFUNGAL AGENT; FATTY ACID; FLUCONAZOLE; OLEIC ACID; PLANT MEDICINAL PRODUCT; TRANSCRIPTION FACTOR; TRANSCRIPTOME; UNCLASSIFIED DRUG;

ANTIFUNGAL ACTIVITY; ANTIFUNGAL SUSCEPTIBILITY; ARTICLE; ASSAY; CANDIDA; CANDIDA ALBICANS; CANDIDIASIS; CHEMICAL ANALYSIS; CONTROLLED STUDY; DRUG MECHANISM; DRUG RESPONSE; FATTY ACID METABOLISM; FATTY ACID OXIDATION; FUNGICIDAL ACTIVITY; FUNGUS GROWTH; FUNGUS HYPHAE; FUNGUS MUTANT; GENE EXPRESSION; GENETIC PROCEDURES; GENETIC TRANSCRIPTION; HOMEOSTASIS; HUMAN; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE;

ALKYNES; ANTIFUNGAL AGENTS; CANDIDA ALBICANS; FATTY ACIDS; FATTY ACIDS, MONOUNSATURATED; FATTY ACIDS, UNSATURATED; FLUCONAZOLE; SACCHAROMYCES CEREVISIAE;

EID: 84861173086     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.05663-11     Document Type: Article

References (59)

1. Agarwal AK, et al. 2008. Role of heme in the antifungal activity of the azaoxoaporphine alkaloid sampangine. Eukaryot. Cell 7:387-400. (Pubitemid 351959706)
2. Berry DE, Chan JA, MacKenzie L, Hecht SM. 1991. 9-Octadecynoic acid: a novel DNA binding agent. Chem. Res. Toxicol. 4:195-198.
3. Bohlmann F. 1988. Naturally occurring acetylenes. Bioactive Mol. 7:1-19.
4. Brondz I, Olsen I. 1990. Fatty acid contents of the yeast and mycelial phase of Candida albicans. J. Chromatogr. 533:152-158.
5. Calderone RA, Fonzi WA. 2001. Virulence factors of Candida albicans. Trends Microbiol. 9:327-335. (Pubitemid 32575277)
6. Carballeira NM. 2008. New advances in fatty acids as antimalarial, anti-mycobacterial and antifungal agents. Prog. Lipid Res. 47:50-61. (Pubitemid 350216622)
7. Chayakulkeeree M, Rude TH, Toffaletti DL, Perfect JR. 2007. Fatty acid synthesis is essential for survival of Cryptococcus neoformans and a potential fungicidal target. Antimicrob. Agents Chemother. 51:3537-3545. (Pubitemid 47519341)
8. Choi JY, Stukey J, Hwang SY, Martin CE. 1996. Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 gene. J. Biol. Chem. 271:3581-3589. (Pubitemid 26065670)
9. CLSI. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A3, 3rd ed. Clinical Laboratory Standards Institute, Wayne, PA.
10. Daum G, et al. 1999. Systematic analysis of yeast strains with possible defects in lipid metabolism. Yeast 15:601-614. (Pubitemid 29221676)
11. de Hoon MJ, Imoto S, Nolan J, Miyano S. 2004. Open source clustering software. Bioinformatics 20:1453-1454. (Pubitemid 38931415)
12. d'Enfert C. 2006. Biofilms and their role in the resistance of pathogenic Candida to antifungal agents. Curr. Drug Targets 7:465-470. (Pubitemid 43744837)
13. Ding MZ, Tian HC, Cheng JS, Yuan YJ. 2009. Inoculum size-dependent interactive regulation of metabolism and stress response of Saccharomyces cerevisiae revealed by comparative metabolomics. J. Biotechnol. 144:279-286.
14. Harbison CT, et al. 2004. Transcriptional regulatory code of a eukaryotic genome. Nature 431:99-104. (Pubitemid 39215116)
15. Kamiryo T, Parthasarathy S, Numa S. 1976. Evidence that acyl coenzyme A synthetase activity is required for repression of yeast acetyl coenzyme A carboxylase by exogenous fatty acids. Proc. Natl. Acad. Sci. U. S. A. 73:386-390.
16. Karpichev IV, Small GM. 1998. Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Mol. Cell Biol. 18:6560-6570. (Pubitemid 28500545)
17. Koerkamp MG, et al. 2002. Dissection of transient oxidative stress response in Saccharomyces cerevisiae by using DNA microarrays. Mol. Biol. Cell 13:2783-2794.
18. Kourtis N, Tavernarakis N. 2009. Autophagy and cell death in model organisms. Cell Death Differ. 16:21-30.
19. Krishnamurthy S, et al. 2004. Dosage-dependent functions of fatty acid desaturase Ole1p in growth and morphogenesis of Candida albicans. Microbiology 150:1991-2003. (Pubitemid 38923697)
20. Lewis RE. 2009. Overview of the changing epidemiology of candidemia. Curr. Med. Res. Opin. 25:1732-1740.
21. Li XC, et al. 2003. Acetylenic acids inhibiting azole-resistant Candida albicans from Pentagonia gigantifolia. J. Nat. Prod. 66:1132-1135.
22. Li XC, et al. 2008. Potent in vitro antifungal activities of naturally occurring acetylenic acids. Antimicrob. Agents Chemother. 52:2442-2448.
23. Lockshon D, Surface LE, Kerr EO, Kaeberlein M, Kennedy BK. 2007. The sensitivity of yeast mutants to oleic acid implicates the peroxisome and other processes in membrane function. Genetics 175:77-91. (Pubitemid 46168556)
24. Mannazzu I, et al. 2008. Behaviour of Saccharomyces cerevisiae wine strains during adaptation to unfavourable conditions of fermentation on synthetic medium: cell lipid composition, membrane integrity, viability and fermentative activity. Int. J. Food Microbiol. 121:84-91. (Pubitemid 350278635)
25. Marchesini S, Poirier Y. 2003. Futile cycling of intermediates of fatty acid biosynthesis toward peroxisomal beta-oxidation in Saccharomyces cerevisiae. J. Biol. Chem. 278:32596-32601. (Pubitemid 37055697)
26. Morbidoni HR, et al. 2006. Dual inhibition of mycobacterial fatty acid biosynthesis and degradation by 2-alkynoic acids. Chem. Biol. 13:297-307.
27. Morgan J. 2005. Global trends in candidemia: review of reports from 1995-2005. Curr. Infect. Dis. Rep. 7:429-439. (Pubitemid 41671586)
28. Murzyn A, Krasowska A, Stefanowicz P, Dziadkowiec D, Lukaszewicz M. 2010. Capric acid secreted by S. boulardii inhibits C. albicans filamentous growth, adhesion and biofilm formation. PLoS One 5:e12050.
29. Nantel A, Rigby T, Hogues H, Whiteway M. 2006. Microarrays for studying pathogenicity in Candida albicans. Wiley Press, Hoboken, NJ.
30. Nguyen LN, Gacser A, Nosanchuk JD. 2011. The stearoyl-coenzyme A desaturase 1 is essential for virulence and membrane stress in Candida parapsilosis through unsaturated fatty acid production. Infect. Immun. 79:136 -145.
31. Nguyen LN, Trofa D, Nosanchuk JD. 2009. Fatty acid synthase impacts the pathobiology of Candida parapsilosis in vitro and during mammalian infection. PLoS One 4:e8421.
32. Nobile CJ, Nett JE, Andes DR, Mitchell AP. 2006. Function of Candida albicans adhesin Hwp1 in biofilm formation. Eukaryot. Cell 5:1604-1610. (Pubitemid 44622591)
33. Ondrey F, Harris JE, Anderson KM. 1989. Inhibition of U937 eicosanoid and DNA synthesis by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism and its partial reversal by leukotriene C4. Cancer Res. 49:1138-1142. (Pubitemid 19074825)
34. Parsons AB, Geyer R, Hughes TR, Boone C. 2003. Yeast genomics and proteomics in drug discovery and target validation. Prog. Cell Cycle Res. 5:159-166.
35. Pasrija R, Panwar SL, Prasad R. 2008. Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts. Antimicrob. Agents Chemother. 52:694-704. (Pubitemid 351170846)
36. Poirier Y, Antonenkov VD, Glumoff T, Hiltunen JK. 2006. Peroxisomal beta-oxidation-a metabolic pathway with multiple functions. Biochim. Biophys. Acta 1763:1413-1426. (Pubitemid 44883386)
37. Ramírez MA, Lorenz MC. 2007. Mutations in alternative carbon utilization pathways in Candida albicans attenuate virulence and confer pleiotropic phenotypes. Eukaryot. Cell 6:280-290.
38. Ramírez MA, Lorenz MC. 2009. The transcription factor homolog CTF1 regulates β-oxidation in Candida albicans. Eukaryot. Cell 8:1604-1614.
39. Rottensteiner H, Kal AJ, Hamilton B, Ruis H, Tabak HF. 1997. A heterodimer of the Zn2Cys6 transcription factors Pip2p and Oaf1p controls induction of genes encoding peroxisomal proteins in Saccharomyces cerevisiae. Eur. J. Biochem. 247:776 -783.
40. Saldanha AJ. 2004. Java Treeview-extensible visualization of microarray data. Bioinformatics 20:3246-3248. (Pubitemid 39619217)
41. Schneider F, Cassagne C. 1995. Specific inhibition of plant fatty acid elongation by a long-chain cerulenin analogue. Eur. J. Biochem. 228:704-709.
42. Shareck J, Belhumeur P. 2011. Modulation of morphogenesis in Candida albicans by various small molecules. Eukaryot. Cell 10:1004-1012.
43. Shareck J, Nantel A, Belhumeur P. 2011. Conjugated linoleic acid inhibits hyphal growth in Candida albicans by modulating Ras1p cellular levels and downregulating TEC1 expression. Eukaryot. Cell 10:565-577.
44. Siddiq A, Dembitsky V. 2008. Acetylenic anticancer agents. Anticancer Agents Med. Chem. 8:132-170. (Pubitemid 351761441)
45. Smith JJ, et al. 2002. Transcriptome profiling to identify genes involved in peroxisome assembly and function. J. Cell Biol. 158:259-271.
46. Smriti Krishnamurthy SS, Prasad R. 1999. Membrane fluidity affects functions of Cdr1p, a multidrug ABC transporter of Candida albicans. FEMS Microbiol. Lett. 173:475-481. (Pubitemid 29146154)
47. Sturgeon CM, Kemmer D, Anderson HJ, Roberge M. 2006. Yeast as a tool to uncover the cellular targets of drugs. Biotechnol. J. 1:289-298.
48. Tasdemir D, et al. 2010. 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. Bioorg. Med. Chem. 18:7475-7485.
49. Tehlivets O, Scheuringer K, Kohlwein SD. 2007. Fatty acid synthesis and elongation in yeast. Biochim. Biophys. Acta 1771:255-270. (Pubitemid 46428612)
50. Teixeira MC, et al. 2006. The YEASTRACT database: a tool for the analysis of transcription regulatory associations in Saccharomyces cerevisiae. Nucleic Acids Res. 34:D446-D451.
51. Toke DA, Martin CE. 1996. Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J. Biol. Chem. 271:18413-18422. (Pubitemid 26322697)
52. White TC. 1997. Increased mRNA levels of ERG16, CDR, and MDR1 correlate with increases in azole resistance in Candida albicans isolates from a patient infected with human immunodeficiency virus. Antimicrob. Agents Chemother. 41:1482-1487. (Pubitemid 27289672)
53. Wimalasena TT, et al. 2008. Impact of the unfolded protein response upon genome-wide expression patterns, and the role of Hac1 in the polarized growth, of Candida albicans. Fungal Genet. Biol. 45:1235-1247.
54. Wisplinghoff H, et al. 2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39:309-317. (Pubitemid 39050477)
55. Wood R, Lee T. 1981. Metabolism of 2-hexadecynoate and inhibition of fatty acid elongation. J. Biol. Chem. 256:12379-12386. (Pubitemid 12141505)
56. Wood R, Lee T, Gershon H. 1980. Effect of methyl 2-hexadecynoate on hepatic fatty acid metabolism. Lipids 15:141-150. (Pubitemid 10054161)
57. Xu D, et al. 2009. Chemical genetic profiling and characterization of small-molecule compounds that affect the biosynthesis of unsaturated fatty acids in Candida albicans. J. Biol. Chem. 284:19754-19764.
58. Zaman S, Lippman SI, Zhao X, Broach JR. 2008. How Saccharomyces responds to nutrients. Annu. Rev. Genet. 42:27-81.
59. Zhao XJ, McElhaney-Feser GE, Sheridan MJ, Broedel SE, Jr, Cihlar RL. 1997. Avirulence of Candida albicans FAS2 mutants in a mouse model of systemic candidiasis. Infect. Immun. 65:829-832. (Pubitemid 27053261)