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Echinocandins: production and applications

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Abstract

The first echinocandin-type antimycotic (echinocandin B) was discovered in the 1970s. It was followed by the isolation of more than 20 natural echinocandins. These cyclic lipo-hexapeptides are biosynthesized on non-ribosomal peptide synthase complexes by different ascomycota fungi. They have a unique mechanism of action; as non-competitive inhibitors of β-1,3-glucan synthase complex they target the fungal cell wall. Results of the structure–activity relationship experiments let us develop semisynthetic derivatives with improved properties. Three cyclic lipohiexapeptides (caspofungin, micafungin and anidulafungin) are currently approved for use in clinics. As they show good fungicidal (Candida spp.) or fungistatic (Aspergillus spp.) activity against the most important human pathogenic fungi including azole-resistant strains, they are an important addition to the antifungal armamentarium. Some evidence of acquired resistance against echinocandins has been detected among Candida glabrata strains in recent years, which enhanced the importance of data collected on the mechanism of acquired resistance developing against the echinocandins. In this review, we show the structural diversity of natural echinocandins, and we summarize the emerging data on their mode of action, biosynthesis and industrial production. Their clinical significance as well as the mechanism of natural and acquired resistance is also discussed.

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References

  • Adefarati AA, Giacobbe RA, Hensens OD, Tkacz JS (1991) Biosynthesis of L-671,329, an echinocandin-type antibiotic produced by Zalerion arboricola: origins of some of the unusual amino acids and the dimethylmyristic acid side-chain. J Am Chem Soc 113:3542–3545

    Article  CAS  Google Scholar 

  • Adefarati AA, Hensens OD, Jones ET, Tkacz JS (1992) Pneumocandins from Zalerion arboricola V. Glutamic acid- and leucinederived amino acids in pneumocandin Ao (l-671,329) and distinct origins of the substituted proline residues in pneumocandins Ao and Bo. J Antibiot 45:1953–1957

    Article  CAS  Google Scholar 

  • Arendrup MC, Perkhofer S, Howard SJ, Garcia-Effron G, Vishukumar A, Perlin D, Lass-Florl C (2008) Establishing in vitro–in vivo correlations for Aspergillus fumigatus: the challenge of azoles versus echinocandins. Antimicrob Agents Chemother 52:3504–3511

    Article  CAS  Google Scholar 

  • Arikan S, Lozano-Chiu M, Paetznick V, Rex JH (2001) In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother 45:327–330

    Article  CAS  Google Scholar 

  • Aszodi J, Fauveau P, Melon-Manguer D, Ehlersb E, Schioa L (2002) Synthesis of new echinocandin derivatives via a diol-keto transposition. Tetrahedron Lett 43:2953–2956

    Article  CAS  Google Scholar 

  • Bachmann SP, VandeWalle K, Ramage G, Patterson TF, Wickes BL, Graybill JR, López-Ribot JL (2002a) In vitro activity of caspofungin against Candida albicans biofilms. Antimicrob Agents Chemother 46:3591–3596

    Article  CAS  Google Scholar 

  • Bachmann SP, Patterson TF, Lopez-Ribot JL (2002b) In vitro activity of caspofungin (MK-0991) against Candida albicans clinical isolates displaying different mechanisms of azole resistance. J Clin Microbiol 40:2228–2230

    Article  CAS  Google Scholar 

  • Bacic A, Fincher GB, Stone BA (2009) Chemistry, biochemistry, and biology of 1–3 beta glucans and related polysaccharides. Academic Press, Amsterdam

    Google Scholar 

  • Bal AM (2010) The echinocandins: three useful choices or three too many? Int J Antimicrob Agents 35:13–18

    Article  CAS  Google Scholar 

  • Balashov SV, Park S, Perlin DS (2006) Assessing resistance to the echinocandin antifungal drug caspofungin in Candida albicans by profiling mutations in FKS1. Antimicrob Agents Chemother 50:2058–2063

    Article  CAS  Google Scholar 

  • Balkovec JM, Black RM, Abruzzo GK, Bartizal K, Dreikorn S, Nollstadt K (1993) Pneumocandin antifungal lipopeptides. The phenolic hydroxyl is required for 1,3- β-D-glucan synthesis inhibition. Bioorg Med Chem Lett 3:2039–2042

    Article  CAS  Google Scholar 

  • Bayegan S, Szilágyi J, Kemény-Beke Á, Földi R, Kardos G, Gesztelyi R, Juhasz B, Adnan A, Majoros L (2011) Efficacy of a single 6 mg/kg versus two 3 mg/kg caspofungin doses for treatment of disseminated candidiasis caused by Candida albicans in a neutropenic mouse model. J Chemother 23:107–109

    CAS  Google Scholar 

  • Ben-Ami R, Garcia-Effron G, Lewis RE, Gamarra S, Leventakos K, Perlin DS, Kontoyiannis DP (2011) Fitness and virulence costs of Candida albicans fks1 hot spot mutations associated with echinocandin resistance. J Infect Dis 204:626–635

    Article  CAS  Google Scholar 

  • Benz F, Knüsel F, Nüesch J, Treichler H, Voser W, Nyfeler R, Keller-Schierlein W (1974) Stoffwechselprodukte von Mikroorganismen 143. Mitteilung. Echinocandin B, ein neuartiges Polypeptid-Antibioticum aus Aspergillus nidulans var. echinulatus: Isolierung und Bausteine. Helv Chim Acta 57:2459–2477

    Article  CAS  Google Scholar 

  • Betts RF, Nucci M, Talwar D, Gareca M, Queiroz-Telles F, Bedimo RJ, Herbrecht R, Ruiz-Palacios G, Young JA, Baddley JW, Strohmaier KM, Tucker KA, Taylor AF, Kartsonis NA; Caspofungin High-Dose Study Group (2009) A Multicenter, double-blind trial of a high-dose caspofungin treatment regimen versus a standard caspofungin treatment regimen for adult patients with invasive candidiasis. Clin Infect Dis 48:1676–1684

    Article  CAS  Google Scholar 

  • Bills GF, Platas G, Peláez F, Masurekar P (1999) Reclassification of a pneumocandin-producing anamorph, Glarea lozoyensis gen. et sp. nov., previously identified as Zalerion arboricola. Mycol Res 103:179–192

    Article  CAS  Google Scholar 

  • Boeck LD, Kastner RE (1981) Method of producing the A-30912 antibiotics. US Pat 4:288–549

    Google Scholar 

  • Bouffard FA, Zambias RA, Dropinski JF, Balkovec JM, Hammond ML, Abruzzo GK, Bartizal KF, Marrinan JA, Kurtz MB, McFadden DC, Nollstadt KH, Powles MA, Schmatz DM (1994) Synthesis and antifungal activity of novel cationic pneumocandin B0 derivatives. J Med Chem 37:222–225

    Article  CAS  Google Scholar 

  • Bowman JC, Hicks PS, Kurtz MB, Rosen H, Schmatz DM, Liberator PA, Douglas CM (2002) The antifungal echinocandin caspofungin acetate kills growing cells of Aspergillus fumigatus in vitro. Antimicrob Agents Chemother 46:3001–3012

    Article  CAS  Google Scholar 

  • Bryskier A (2005) Peptide antibiotics. In: Bryskier A (ed) Antimicrobial agents: Antibacterials and antifungals. ASM Press, Washington, pp 826–879

  • Cacho RA, Jiang W, Chooi YH, Walsh CT, Tang Y (2012) Identification and characterization of the echinocandin B biosynthetic gene cluster from Emericella rugulosa NRRL 11440. J Am Chem Soc 134:16781–16790

    Article  CAS  Google Scholar 

  • Calvo E, Pastor FJ, Mayayo E, Guarro J (2011) Efficacy of anidulafungin against Aspergillus niger in vitro and in vivo. Int J Antimicrob Agents 38:360–363

    Google Scholar 

  • Calvo E, Pastor FJ, Salas V, Mayayo E, Guarro J (2012) Combined therapy of voriconazole and anidulafungin in murine infections by Aspergillus flavus. Mycopathologia 173:251–257

    Google Scholar 

  • Cassone A, Mason R, Kerridge D (1981) Lysis of growing yeast-form cells of Candida albicans by echinocandin: a cytological study. Sabouraudia 19:97–110

    Article  CAS  Google Scholar 

  • Chamilos G, Lewis RE, Albert N, Kontoyiannis DP (2007) Paradoxical effect of echinocandins across Candida species in vitro: evidence for echinocandin-specific and Candida species-related differences. Antimicrob Agents Chemother 51:2257–2259

    Article  CAS  Google Scholar 

  • Chandrasekar PH, Sobel JD (2006) Micafungin: a new echinocandin. Clin Infect Dis 42:1171–1178

    Google Scholar 

  • Chen SC, Slavin MA, Sorrell TC (2011) Echinocandin antifungal drugs in fungal infections: a comparison. Drugs 71:11–41

    Article  CAS  Google Scholar 

  • Clancy CJ, Huang H, Cheng SH, Derendorf H, Nguyen MH (2006) Characterizing the effects of caspofungin on Candida albicans, Candida parapsilosis, and Candida glabrata isolates by simultaneous time-kill and postantifungal-effect experiments. Antimicrob Agents Chemother 50:2569–2572

    Article  CAS  Google Scholar 

  • Clemons KV, Espiritu M, Parmar R, Stevens DA (2006) Assessment of paradoxical effect of caspofungin in therapy of candidiasis. Antimicrob Agents Chemother 50:1293–1297

    Article  CAS  Google Scholar 

  • Connors N, Pollard D (2004) Pneumocandin B0 production by fermentation of the fungus Glarea lozoyensis. In: Zhiqiang A (ed) Handbook of Industrial Mycology. Marcel Dekker, New York, pp 515–538

    Chapter  Google Scholar 

  • Connors N, Petersen L, Hughes R, Saini K, Olewinski R, Salmon P (2000) Residual fructose and osmolality affect the levels of pneumocandins B0 and C0 produced by Glarea lozoyensis. Appl Microbiol Biotechnol 54:814–818

    Article  CAS  Google Scholar 

  • Cushion MT, Collins MS (2011) Susceptibility of Pneumocystis to echinocandins in suspension and biofilm cultures. Antimicrob Agents Chemother 55:4513–4518

    Article  CAS  Google Scholar 

  • De Rosa FG, Garazzino S, Pasero D, Di Perri G, Ranieri VM (2009) Invasive candidiasis and candidemia: new guidelines. Minerva Anestesiol 75:453–458

    Google Scholar 

  • Debono M, Gordee RS (1994) Antibiotics that inhibit fungal cell wall development. Annu Rev Microbiol 48:471–497

    Article  CAS  Google Scholar 

  • Debono M, Abbott BJ, Turner JR, Howard LC, Gordee RS, Hunt AS, Barnhart M, Molloy RM, Willard KE, Fukuda D, Butler TF, Zeckner DJ (1988) Synthesis and evaluation of LY121019, a member of a series of semisynthetic analogues of the antifungal lipopeptide echinocandin B. Ann N Y Acad Sci 544:152–167

    Article  CAS  Google Scholar 

  • Debono M, Abbott BJ, Fukuda DS, Barnhart M, Willard KE, Molloy RM, Michel KH, Turner JR, Butler TF, Hunt AH (1989) Synthesis of new analogs of echinocandin B by enzymatic deacylation and chemical reacylation of the echinocandin B peptide: synthesis of the antifungal agent cilofungin (LY121019). J Antibiot 42:389–397

    Article  CAS  Google Scholar 

  • Debono M, Turner WW, LaGrandeur L, Burkhardt FJ, Nissen JS, Nichols KK, Rodriguez MJ, Zweifel MJ, Zeckner DJ, Gordee RS, Tang J, Parr TR (1995) Semisynthetic chemical modification of the antifungal lipopeptide echinocandin B (ECB): structure–activity studies of the lipophilic and geometric parameters of polyarylated acyl analogs of ECB. J Med Chem 38:3271–3281

    Article  CAS  Google Scholar 

  • Dichtl K, Helmschrott C, Dirr F, Wagener J (2012) Deciphering cell wall integrity signalling in Aspergillus fumigatus: identification and functional characterization of cell wall stress sensors and relevant Rho GTPases. Mol Microbiol 83:506–519

    Article  CAS  Google Scholar 

  • DiDone L, Oga D, Krysan DJ (2011) A novel assay of biofilm antifungal activity reveals that amphotericin B and caspofungin lyse Candida albicans cells in biofilms. Yeast 28:561–568

    Article  CAS  Google Scholar 

  • Douglas CM (2006) Understanding the microbiology of the Aspergillus cell wall and the efficacy of caspofungin. Med Mycol 44:S95–S99

    Article  CAS  Google Scholar 

  • Douglas CM, D’Ippolito JA, Shei GJ, Meinz M, Onishi J, Marrinan JA, Li W, Abruzzo GK, Flattery A, Bartizal K, Mitchell A, Kurtz MB (1997) Identification of the FKS1 gene of Candida albicans as the essential target of 1,3-beta-D-glucan synthase inhibitors. Antimicrob Agents Chemother 41:2471–2479

    CAS  Google Scholar 

  • Drouhet E, Dupont B, Improvisi L, Lesourd M, Prevost MC (1990) Activity of cilofungin (LY 121019), a new lipopeptide antibiotic, on the cell wall and cytoplasmic membrane of Candida albicans. Structural modifications in scanning and transmission electron microscopy. J Med Vet Mycol 28:425–436

    Article  CAS  Google Scholar 

  • Espinel-Ingroff A (2003) In vitro antifungal activities of anidulafungin and micafungin, licensed agents and the investigational triazole posaconazole as determined by NCCLS methods for 12,052 fungal isolates: review of the literature. Rev Iberoam Micol 20:121–136

    Google Scholar 

  • Földi R, Szilágyi J, Kardos G, Berényi R, Kovács R, Majoros L (2012) Effect of 50 % human serum on the killing activity of micafungin against eight Candida species using time-kill methodology. Diagn Microbiol Infect Dis 73:338–342

    Article  CAS  Google Scholar 

  • Fortwendel JR, Juvvadi PR, Perfect BZ, Rogg LE, Perfect JR, Steinbach WJ (2010) Transcriptional regulation of chitin synthases by calcineurin controls paradoxical growth of Aspergillus fumigatus in response to caspofungin. Antimicrob Agents Chemother 54:1555–1563

    Google Scholar 

  • Fujie A (2007) Discovery of micafungin (FK463): a novel antifungal drug derived from a natural product lead. Pure Appl Chem 79:603–614

    Article  CAS  Google Scholar 

  • Fujie A, Iwamoto T, Sato B, Muramatsu H, Kasahara C, Furuta T, Hori Y, Hino M, Hashimoto S (2001) FR131535, a novel water-soluble echinocandin-like lipopeptide: synthesis and biological properties. Bioorg Med Chem Lett 11:399–402

    Article  CAS  Google Scholar 

  • Ganesan LT, Manavathu EK, Cutright JL, Alangaden GJ, Chandrasekar PH (2004) In-vitro activity of nikkomycin Z alone and in combination with polyenes, triazoles or echinocandins against Aspergillus fumigatus. Clin Microbiol Infect 10:961–966

    Article  CAS  Google Scholar 

  • Gao X, Haynes SW, Ames BD, Wang P, Vien L, Walsh CT, Tang Y (2012) Cyclization of fungal nonribosomal peptides by a terminal condensation-like domain. Nat Chem Biol 8:823–830

    Article  CAS  Google Scholar 

  • Garcia-Effron G, Katiyar SK, Park S, Edlind TD, Perlin DS (2008) A naturally occurring proline-to-alanine amino acid change in Fks1p in Candida parapsilosis, Candida orthopsilosis, and Candida metapsilosis accounts for reduced echinocandin susceptibility. Antimicrob Agents Chemother 52:2305–2312

    Article  CAS  Google Scholar 

  • Garcia-Effron G, Lee S, Park S, Cleary JD, Perlin DS (2009a) Effect of Candida glabrata FKS1 and FKS2 mutations on echinocandin sensitivity and kinetics of 1,3-(beta)-D-glucan synthase: implication for the existing susceptibility breakpoint. Antimicrob Agents Chemother 53:3690–3699

    Article  CAS  Google Scholar 

  • Garcia-Effron G, Park S, Perlin DS (2009b) Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. Antimicrob Agents Chemother 53:112–122

    Article  CAS  Google Scholar 

  • Garcia-Effron GS, Park S, Perlin DS (2011) Improved detection of Candida sp. fks hot spot mutants by using the method of the CLSI M27-A3 Document with the addition of bovine serum albumin. Antimicrob Agents Chemother 55:2245–2255

    Article  CAS  Google Scholar 

  • Gardiner RE, Souteropoulos P, Park S, Perlin DS (2005) Characterization of Aspergillus fumigatus mutants with reduced susceptibility to caspofungin. Med Mycol 43:S299–S305

    Article  CAS  Google Scholar 

  • Geiser DM, Klich MA, Frisvad JC, Peterson SW, Varga J, Samson RA (2007) The current status of species recognition and identification in Aspergillus. Stud Mycol 59:1–10

    Article  CAS  Google Scholar 

  • Ghannoum M, D’Angelo M (2005) Anidulafungin: a potent antifungal that targets candida and aspergillus. Infect Dis Clin Prac 13:165–178

    Article  Google Scholar 

  • Gil C, Pérez-Diaz R, Nombela C (1994) Inhibitory and morphological effects of several antifungal agents on three types of Candida albicans morphological mutants. J Med Vet Mycol 32:151–162

    Article  CAS  Google Scholar 

  • Gordee RS, Zeckner DJ, Howard LC, Alborn WE Jr, Debono M (1988) Anti-Candida activity and toxicology of LY121019, a novel semisynthetic polypeptide antifungal antibiotic. Ann N Y Acad Sci 544:294–309

    Article  CAS  Google Scholar 

  • Hansen DB, Bumpus SB, Aron ZD, Kelleher NL, Walsh CT (2007) The loading module of mycosubtilin: an adenylation domain with fatty acid selectivity. J Am Chem Soc 129:6366–6367

    Article  CAS  Google Scholar 

  • Hao B, Cheng S, Clancy CJ, Nguyen MH (2012) Caspofungin kills Candida albicans by causing both cellular apoptosis and necrosis. Antimicrob Agents Chemother. doi:10.1128/AAC.01366-12

  • Hensens OD, Liesch JM, Zink DL, Smith JL, Wichmann CF, Schwartz RE (1992) Pneumocandins from Zalerion arboricola. III. Structure elucidation. J Antibiot 45:1875–1885

    Article  CAS  Google Scholar 

  • Hino M, Fujie A, Iwamoto T, Hori Y, Hashimoto M, Tsurumi Y, Sakamoto K, Takase S, Hashimoto S (2001) Chemical diversity in lipopeptide antifungal antibiotics. J Ind Microbiol Biotechnol 27:157–162

    Article  CAS  Google Scholar 

  • Hodges RL, Hodges DW, Goggans K, Xuei X, Skatrud P, McGilvray D (1994) Genetic modification of an echinocandin B-producing strain of Aspergillus nidulans to produce mutants blocked in sterigmatocystin biosynthesis. J Ind Microbiol 13:372–381

    Article  CAS  Google Scholar 

  • Hodges RL, Kelkar HS, Xuei X, Skatrud PL, Keller NP, Adams TH, Kaiser RE, Vinci VA, McGilvray D (2000) Characterization of an echinocandin B-producing strain blocked for sterigmatocystin biosynthesis reveals a translocation in the stcW gene of the aflatoxin biosynthetic pathway. J Ind Microbiol Biotechnol 25:333–341

    Article  CAS  Google Scholar 

  • Hoffmann D, Hevel JM, Moore RE, Moore BS (2003) Sequence analysis and biochemical characterization of the nostopeptolide A biosynthetic gene cluster from Nostoc sp. GSV224. Gene 311:171–180

    Article  CAS  Google Scholar 

  • Hormigo D, de la Mata I, Acebal C, Arroyo M (2010) Immobilized aculeacin A acylase from Actinoplanes utahensis: characterization of a novel biocatalyst. Bioresour Technol 101:4261–4268

    Article  CAS  Google Scholar 

  • Howard SJ, Arendrup MC (2011) Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection. Med Mycol 49:S90–S95

    Article  CAS  Google Scholar 

  • Imtiaz T, Lee KK, Munro CA, Maccallum DM, Shankland GS, Johnson EM, Macgregor MS, Bal AM (2012) Echinocandin resistance due to simultaneous FKS mutation and increased cell wall chitin in a Candida albicans bloodstream isolate following brief exposure to caspofungin. J Med Microbiol 61:1330–1334

    Article  CAS  Google Scholar 

  • Inokoshi J, Takeshima H, Ikeda H, Omura S (1992) Cloning and sequencing of the aculeacin A acylase-encoding gene from Actinoplanes utahensis and expression in Streptomyces lividans. Gene 119:29–35

    Article  CAS  Google Scholar 

  • Ishihara S, Hirata A, Nogami S, Beauvais A, Latge JP, Ohya Y (2007) Homologous subunits of 1,3-beta-glucan synthase are important for spore wall assembly in Saccharomyces cerevisiae. Eukaryot Cell 6:143–156

    Article  CAS  Google Scholar 

  • Iwamoto T, Fujie A, Sakamoto K, Tsurumi Y, Shigematsu N, Yamashita M, Hashimoto S, Okuhara M, Kohsaka M (1994) WF11899A, B and C, novel antifungal lipopeptides, I: taxonomy, fermentation, isolation and physico-chemical properties. J Antibiot 47:1084–1091

    Article  CAS  Google Scholar 

  • Johnson ME, Katiyar SK, Edlind TD (2011) New Fks hot spot for acquired echinocandin resistance in Saccharomyces cerevisiae and its contribution to intrinsic resistance of Scedosporium species. Antimicrob Agents Chemother 55:3774–3781

    Article  CAS  Google Scholar 

  • Kanafani ZA, Perfect JR (2008) Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin Infect Dis 46:120–128

    Article  Google Scholar 

  • Kanasaki R, Abe F, Kobayashi M, Katsuoka M, Hashimoto M, Takase S, Tsurumi Y, Fujie A, Hino M, Hashimoto S, Hori Y (2006a) FR220897 and FR220899, novel antifungal lipopeptides from Coleophoma empetri no. 14573. J Antibiot 59:149–157

    Article  CAS  Google Scholar 

  • Kanasaki R, Kobayashi M, Fujine K, Sato I, Hashimoto M, Takase S, Tsurumi Y, Fujie A, Hino M, Hashimoto S, Hori Y (2006b) FR227673 and FR190293, novel antifungal lipopeptides from Chalara sp. No. 22210 and Tolypocladium parasiticum No. 16616. J Antibiot 59:158–167

    Article  CAS  Google Scholar 

  • Kanasaki R, Sakamoto K, Hashimoto M, Takase S, Tsurumi Y, Fujie A, Hino M, Hashimoto S, Hori Y (2006c) FR209602 and related compounds, novel antifungal lipopeptides from Coleophoma crateriformis no.738. I. Taxonomy, fermentation, isolation and physico-chemical properties. J Antibiot 59:137–144

    Article  CAS  Google Scholar 

  • Kanda M, Tsuboi M, Sakamoto K, Shimizu S, Yamashita M, Honda H (2009) Improvement of FR901379 production by mutant selection and medium optimization. J Biosci Bioeng 107:530–534

    Article  CAS  Google Scholar 

  • Kanda M, Yamamoto E, Hayashi A, Yabutani T, Yamashita M, Honda H (2010) Scale-up fermentation of echinocandin type antibiotic FR901379. J Biosci Bioeng 109:138–144

    Article  CAS  Google Scholar 

  • Katiyar S, Pfaller M, Edlind T (2006) Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility. Antimicrob Agents Chemother 50:2892–2894

  • Katiyar SK, Edlind TD (2009) Role for Fks1 in the intrinsic echinocandin resistance of Fusarium solani as evidenced by hybrid expression in Saccharomyces cerevisiae. Antimicrob Agents Chemother 53:1772–1778

    Article  CAS  Google Scholar 

  • Katiyar SK, Alastruey-Izquierdo A, Healey KR, Johnson ME, Perlin DS, Edlind TD (2012) Fks1 and Fks2 are functionally redundant but differentially regulated in Candida glabrata: implications for echinocandin resistance. Antimicrob Agents Chemothe 56:6304–6309

    Article  CAS  Google Scholar 

  • Kauss H, Jeblick W (1986) Influence of free fatty acids, lysophosphatidylcholine, platelet-activating factor, acylcarnitine, and echinocandin B on 1,3-beta-D-glucan synthase and callose synthesis. Plant Physiol 80:7–13

    Article  CAS  Google Scholar 

  • Keller-Juslén C, Kuhn M, Loosli HR, Petcher TJ, Weber HP, von Wartburg A (1976) Struktur des cyclopeptid-antibiotikums sl 7810 (= echinocandinb). Tetrahedron Lett 17:4147–4150

    Article  Google Scholar 

  • Klein LL, Li L, Chen HJ, Curty CB, DeGoey DA, Grampovnik DJ, Leone CL, Thomas SA, Yeung CM, Funk KW, Kishore V, Lundell EO, Wodka D, Meulbroek JA, Alder JD, Nilius AM, Lartey PA, Plattner JJ (2000) Total synthesis and antifungal evaluation of cyclic aminohexapeptides. Bioorg Med Chem 8:1677–1696

    Article  CAS  Google Scholar 

  • Klich M, Mendoza C, Mullaney E, Keller N, Bennett JW (2001) A new sterigmatocystin-producing Emericella variant from agricultural desert soils. Syst Appl Microbiol 24:131–138

    Article  CAS  Google Scholar 

  • Kofla G, Ruhnke M (2011) Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature. Eur J Med Res 16:159–166

    Article  CAS  Google Scholar 

  • Kraas FI, Helmetag V, Wittmann M, Strieker M, Marahiel MA (2010) Functional dissection of surfactin synthetase initiation module reveals insights into the mechanism of lipoinitiation. Chem Biol 17:872–880

    Article  CAS  Google Scholar 

  • Kurtz MB, Douglas C, Marrinan J, Nollstadt K, Onishi J, Dreikorn S, Milligan J, Mandala S, Thompson J, Balkovec JM, Bouffard FA, Dropinski JF, Hammond ML, Zambias RA, Abruzzo G, Bartizal K, McManus OB, Garcia ML (1994a) Increased antifungal activity of L-733,560, a water-soluble, semisynthetic pneumocandin, is due to enhanced inhibition of cell wall synthesis. Antimicrob Agents Chemother 38:2750–2757

    Article  CAS  Google Scholar 

  • Kurtz MB, Heath IB, Marrinan J, Dreikorn S, Onishi J, Douglas C (1994b) Morphological effects of lipopeptides against Aspergillus fumigatus correlate with activity against (1,3)-β-D-glucan synthase. Antimicrob Agents Chemother 38:1480–1489

    Article  CAS  Google Scholar 

  • Lal B, Gund VG, Gangopadhyay AK, Nadkarni SR, Dikshit V, Chatterjee DK, Shirvaikar R (2003) Semisynthetic modifications of hemiaminal function at ornithine unit of mulundocandin, towards chemical stability and antifungal activity. Bioorg Med Chem 11:5189–5198

    Article  CAS  Google Scholar 

  • Lamoth F, Juvvadi PR, Gehrke C, Steinbach WJ (2012) In vitro activity of calcineurin and heat-shock protein 90 (HSP90) inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains. Antimicrob Agents Chemother. doi:10.1128/AAC.01857-12

  • Lee KK, Maccallum DM, Jacobsen MD, Walker LA, Odds FC, Gow NA, Munro CA (2012) Elevated cell wall chitin in Candida albicans confers echinocandin resistance in vivo. Antimicrob Agents Chemother 56:208–217

    Article  CAS  Google Scholar 

  • Leonard WR Jr, Belyk KM, Conlon DA, Bender DR, DiMichele LM, Liu J, Hughes DL (2007) Synthesis of the antifungal beta-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0. J Org Chem 72:2335–2343

    Article  CAS  Google Scholar 

  • Maligie MA, Selitrennikoff CP (2005) Cryptococcus neoformans resistance to echinocandins: (1,3)beta-glucan synthase activity is sensitive to echinocandins. Antimicrob Agents Chemother 49:2851–2856

    Article  CAS  Google Scholar 

  • Martos AI, Romero A, González MT, González A, Serrano C, Castro C, Pemán J, Cantón E, Martín-Mazuelos E (2010) Evaluation of the Etest method for susceptibility testing of Aspergillus spp. and Fusarium spp. to three echinocandins. Med Mycol 48:858–861

  • Masurekar PS, Fountoulakis JM, Hallada TC, Sosa MS, Kaplan L (1992) Pneumocandins from Zalerion arboricola. II. Modification of product spectrum by mutation and medium manipulation. J Antibiot 45:1867–1874

    Article  CAS  Google Scholar 

  • Mazur P, Morin N, Baginsky W, el Sherbeini M, Clemas JA, Nielsen JB, Foor F (1995) Differential expression and function of two homologous subunits of yeast 1,3-beta-D-glucan synthase. Mol Cell Biol 15:5671–5681

    CAS  Google Scholar 

  • Mishra BB, Tiwari VK (2011) 1. Natural products in drug discovery: clinical evaluations and investigations. In: Tiwari VK, Mishra BB (eds) Opportunity, challenge and scope of natural products in medicinal chemistry. Research Signpost, Kerala, pp 1–62

    Google Scholar 

  • Mizoguchi J, Saito T, Mizuno K, Hayano K (1977) On the mode of action of the new antifungal agent, aculeacin A: inhibition of cell wall synthesis in Saccharomyces cerevisiae. J Antibiot 30:308–313

    Article  CAS  Google Scholar 

  • Mizuno K, Yagi A, Satoi S, Takada M, Hayashi M, Asano K, Matsuda T (1977) Studies I. Isolation and characterization of aculeacin A. J Antibiot 30:297–302

    Article  CAS  Google Scholar 

  • Morris SA, Schwartz RE, Sesin DF, Masurekar P, Hallada TC, Schmatz DM, Bartizal K, Hensens OD, Zink DL (1994) Pneumocandin D0, a new antifungal agent and potent inhibitor of Pneumocystis carinii. J Antibiot 47:755–764

    Article  CAS  Google Scholar 

  • Mukherjee PK, Sheehan D, Puzniak L, Schlamm H, Ghannoum MA (2011) Echinocandins: are they all the same? J Chemother 23:319–325

    CAS  Google Scholar 

  • Mukhopadhyay T, Ganguli BN, Fehlhaber HW, Kogler H, Verfesy L (1987) Mulundocandin, a new lipopeptide antibiotic. II. Structure elucidation. J Antibiot 40:281–289

    Article  CAS  Google Scholar 

  • Mukhopadhyay T, Roy K, Bhat RG, Sawant SN, Blumbach J, Gangtjli BN, Fehlhaber HW (1992) Deoxymulundocandin-A new echinocandin type antifungal antibiotic. J Antibiot 45:618–623

    Article  CAS  Google Scholar 

  • Niimi K, Maki K, Ikeda F, Holmes AR, Lamping E, Niimi M, Monk BC, Cannon RD (2006) Overexpression of Candida albicans CDR1, CDR2, or MDR1 does not produce significant changes in echinocandin susceptibility. Antimicrob Agents Chemother 50:1148–1155

    Article  CAS  Google Scholar 

  • Nobel HM, Langley D, Sidebottom PJ, Lane SJ, Fisher PJ (1991) An echinocandin from an endophytic Cryptosporiopsis sp. and Pezicula sp. In Pinus sylvestris and Fagus sylvatica. Mycol Res 95:1439–1440

    Article  Google Scholar 

  • Nyfeler R, Keller SW (1974) Metabolites of microorganisms, 143: echinocandin B, a novel polypeptide-antibiotic from Aspergillus nidulans var echinulatus—isolation and structural components. Helv Chim Acta 57:2459–2477

    Article  CAS  Google Scholar 

  • Odabasi Z, Paetznick V, Rex JH, Ostrosky-Zeichner L (2007) Effects of serum on in vitro susceptibility testing of echinocandins. Antimicrob Agents Chemother 51:4214–4216

    Article  CAS  Google Scholar 

  • Paderu P, Park S, Perlin DS (2004) Caspofungin uptake is mediated by a high-affinity transporter in Candida albicans. Antimicrob Agents Chemother 48:3845–3849

    Article  CAS  Google Scholar 

  • Paderu P, Garcia-Effron G, Balashov S, Delmas G, Park S, Perlin DS (2007) Serum differentially alters the antifungal properties of echinocandin drugs. Antimicrob Agents Chemother 51:2253–2256

    Article  CAS  Google Scholar 

  • Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD (2009) Infectious Diseases Society of America: Clinical Practice Guidelines for the management of candidiasis: update by the Infectious Diseases Society of America. Clin Infect Dis 48:503–535

    Article  CAS  Google Scholar 

  • Park S, Kelly R, Kahn JN, Robles J, Hsu MJ, Register E, Li W, Vyas V, Fan H, Abruzzo G, Flattery A, Gill C, Chrebet G, Parent SA, Kurtz M, Teppler H, Douglas CM, Perlin DS (2005) Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother 49:3264–3273

    Article  CAS  Google Scholar 

  • Perez P, Varona R, Garcia-Acha I, Duran A (1981) Effect of papulacandin B and aculeacin A on [Beta]-(1,3)-glucan-synthase from Geotrichum lactis. FEBS Lett 129:249–252

    Article  CAS  Google Scholar 

  • Perlin DS (2007) Resistance to echinocandin-class antifungal drugs. Drug Resist Updat 10:121–130

    Article  CAS  Google Scholar 

  • Perlin DS (2011) Current perspectives on echinocandin class drugs. Future Microbiol 6:441–457

    Article  CAS  Google Scholar 

  • Petersen LA, Hughes DL, Hughes R, DiMichele L, Salmon P, Connors N (2001) Effects of amino acid and trace element supplementation on pneumocandin production by Glarea lozoyensis: impact on titer, analogue levels, and the identification of new analogues of pneumocandin B(0). J Ind Microbiol Biotechnol 26:216–221

    Article  CAS  Google Scholar 

  • Petersen LA, Olewinski R, Salmon P, Connors N (2003) Novel proline hydroxylase activities in the pneumocandin-producing fungus Glarea lozoyensis responsible for the formation of trans 3- and trans 4-hydroxyproline. Appl Microbiol Biotechnol 62:263–267

    Article  CAS  Google Scholar 

  • Peterson SW (2008) Phylogenetic analysis of Aspergillus species using DNA sequences from four loci. Mycologia 100:205–226

    Article  CAS  Google Scholar 

  • Petraitiene R, Petraitis V, Groll AH, Candelario M, Sein T, Bell A, Lyman CA, McMillian CL, Bacher J, Walsh TJ (1999) Antifungal activity of LY303366, a novel echinocandin B, in experimental disseminated candidiasis in rabbits. Antimicrob Agents Chemother 43:2148–2155

    CAS  Google Scholar 

  • Pfaller MA (2012) Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med 125:S3–S13

    Article  CAS  Google Scholar 

  • Pfaller MA, Diekema DJ (2009) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163

    Article  CAS  Google Scholar 

  • Pfaller M, Riley J, Koerner T (1989) Effect of cilofungin (LY121019) on carbohydrate and sterol composition of Candida albicans. Eur J Clin Microbiol Infect Dis 8:1067–1070

    Article  CAS  Google Scholar 

  • Pfaller MA, Castanheira M, Messer SA, Moet GJ, Jones RN (2011a) Echinocandin and triazole antifungal susceptibility profiles for Candida spp., Cryptococcus neoformans, and Aspergillus fumigatus: application of new CLSI clinical breakpoints and epidemiologic cutoff values to characterize resistance in the SENTRY Antimicrobial Surveillance Program (2009). Diagn Microbiol Infect Dis 69:45–50

    Article  CAS  Google Scholar 

  • Pfaller MA, Diekema DJ, Andes D, Arendrup MC, Brown SD, Lockhart SR, Motyl M, Perlin DS, the CLSI Subcommittee for Antifungal Testing (2011b) Clinical breakpoints for the echinocandins and Candida revisited: integration of molecular, clinical, and microbiological data to arrive at species-specific interpretive criteria. Drug Resist Updat 14:164–176

    Article  CAS  Google Scholar 

  • Pfaller MA, Castanheira M, Lockhart SR, Ahlquist AM, Moet GJ, Messer SA, Woosley LN, Jones RN (2012) Frequency of decreased susceptibility and resistance to echinocandins among fluconazole-resistant bloodstream isolates of Candida glabrata: results from the SENTRY Antimicrobial Surveillance Program (2006–2010) and the Centers for Disease Control and Prevention Population-Based Surveillance (2008–2010). J Clin Microbiol. doi:10.1128/JCM.06112-11

  • Plaine A, Walker L, Da Costa G, Mora-Montes HM, McKinnon A, Gow NA, Gaillardin C, Munro CA, Richard ML (2008) Functional analysis of Candida albicans GPI-anchored proteins: roles in cell wall integrity and caspofungin sensitivity. Fungal Genet Biol 45:1404–1414

    Article  CAS  Google Scholar 

  • Pollard DJ, Kirschner TF, Hernandez D, Hunt G, Olewinski R (2002) Pilot-scale process sensitivity studies for the scaleup of a fungal fermentation for the production of Pneumocandins. Biotechnol Bioeng 78:270–279

    Article  CAS  Google Scholar 

  • Pollard DJ, Kirschner TF, Hunt GR, Tong IT, Stieber R, Salmon PM (2007) Scale up of a viscous fungal fermentation. application of scale-up criteria with regime analysis and operating boundary conditions. Biotechnol Bioeng 96:307–317

    Article  CAS  Google Scholar 

  • Radding JA, Heidler SA, Turner W (1998) Photoaffinity analog of the semisynthetic echinocandin LY303366: identification of echinocandin targets in Candida albicans. Antimicrob Agents Chemother 42:1187–1194

    CAS  Google Scholar 

  • Rank C, Nielsen KF, Larsen TO, Varga J, Samson RA, Frisvad JC (2011) Distribution of sterigmatocystin in filamentous fungi. Fungal Biol 115:406–420

    Article  CAS  Google Scholar 

  • Rocha EM, Garcia-Effron G, Park S, Perlin DS (2007) A Ser678Pro substitution in Fks1p confers resistance to echinocandin drugs in Aspergillus fumigatus. Antimicrob Agents Chemother 51:4174–4176

    Article  CAS  Google Scholar 

  • Romano J, Nimrod G, Ben-Tal N, Shadkchan Y, Baruch K, Sharon H, Osherov N (2006) Disruption of the Aspergillus fumigatus ECM33 homologue results in rapid conidial germination, antifungal resistance and hypervirulence. Microbiology 152:1919–1928

    Article  CAS  Google Scholar 

  • Roy K, Mukhopadhyay T, Reddy GC, Desikan KR, Ganguli BN (1987) Mulundocandin, a new lipopeptide antibiotic. I. Taxonomy, fermentation, isolation and characterization. J Antibiot 40:275–280

    Article  CAS  Google Scholar 

  • Rüping MJGD, Vehreschild JJ, Cornely OA (2008) Patients at high risk of invasive fungal infections-when at how to treat. Drugs 68:1941–1962

    Article  Google Scholar 

  • Satoi S, Yagi A, Asano K, Mizuno K, Watanabe T (1977) Studies on aculeacin. II. Isolation and characterization of aculeacins B, C, D, E, F and G. J Antibiot 30:303–307

    Article  CAS  Google Scholar 

  • Sawistowska-Schröder ET, Kerridge D, Perry H (1984) Echinocandin inhibition of 1,3-beta-D-glucan synthase from Candida albicans. FEBS Lett 173:134–138

    Article  Google Scholar 

  • Schmatz DM, Abruzzo G, Powles MA, McFadden DC, Balkovec JM, Black RM, Nollstadt K, Bartizal K (1992) Pneumocandins from Zalerion arboricola. IV. Biological evaluation of natural and semisynthetic pneumocandins for activity against Pneumocystis carinii and Candida species. J Antibiot 45:1886–1891

    Article  CAS  Google Scholar 

  • Schwartz RE, Giacobbe RA, Bland JA, Monaghan RL (1989) L-671,329, a new antifungal agent. I. Fermentation and isolation. J Antibiot 42:163–167

    Article  CAS  Google Scholar 

  • Schwartz RE, Sesin DF, Joshua H, Wilson KE, Kempf AJ, Goklen KA, Kuehner D, Gailliot P, Gleason C, White R, Inamine E, Bills G, Salmon P, Zitano L (1992) Pneumocandins from Zalerion arboricola. Discovery and isolation I. J Antibiot 45:1853–1866

    Article  CAS  Google Scholar 

  • Scott LJ (2012) Micafungin: a review of its use in the prophylaxis and treatment of invasive Candida infections. Drugs 72:2141–2165

    Article  CAS  Google Scholar 

  • Shields RK, Nguyen MH, Press E, Clancy CJ (2011a) Five-minute exposure to caspofungin results in prolonged post-antifungal effects and eliminates the paradoxical growth of Candida albicans. Antimicrob Agents Chemother 55:3598–36023

    Article  CAS  Google Scholar 

  • Shields RK, Nguyen MH, Du C, Press E, Cheng S, Clancy CJ (2011b) Paradoxical effect of caspofungin against Candida bloodstream isolates is mediated by multiple pathways but eliminated in human serum. Antimicrob Agents Chemother 55:2641–2647

    Article  CAS  Google Scholar 

  • Singh SD, Robbins N, Zaas AK, Schell WA, Perfect JR, Cowen LE (2009) Hsp90 governs echinocandin resistance in the pathogenic yeast Candida albicans via calcineurin. PLoS Pathog 5:e1000532

    Article  CAS  Google Scholar 

  • Singh-Babak SD, Babak T, Diezmann S, Hill JA, Xie JL, Chen YL, Poutanen SM, Rennie RP, Heitman J, Cowen LE (2012) Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata. PLoS Pathog 8:e1002718

    Article  CAS  Google Scholar 

  • Sóczó G, Kardos G, Varga I, Kelentey B, Gesztelyi R, Majoros L (2007) In vitro study of Candida tropicalis isolates exhibiting paradoxical growth in the presence of high concentrations of caspofungin. Antimicrob Agents Chemother 51:4474–4476

    Article  CAS  Google Scholar 

  • Stevens DA, Ichinomiya M, Koshi Y, Horiuchi H (2006) Escape of Candida from caspofungin inhibition at concentrations above the MIC (paradoxical effect) accomplished by increased cell wall chitin; evidence for beta-1,6-glucan synthesis inhibition by caspofungin. Antimicrob Agents Chemother 50:3160–3161

    Article  CAS  Google Scholar 

  • Stone BA, Clarke AE (1992) The chemistry and biology of (13)-β-glucans. La Trobe University Press, Melbourne

    Google Scholar 

  • Strobel GA, Miller RV, Martinez-Miller C, Condron MM, Teplow DB, Hess WM (1999) Cryptocandin, a potent antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Microbiology 145:1919–1926

    Article  CAS  Google Scholar 

  • Szilágyi J, Földi R, Bayegan S, Kardos G, Majoros L (2012) Effect of nikkomycin Z and 50 % human serum on the killing activity of high-concentration caspofungin against Candida species using time-kill methodology. J Chemother 24:18–25

    Google Scholar 

  • Taft CS, Stark T, Sellitrennikoff CP (1988) Cilofungin (LYI21019) inhibits Neurospora crassa growth and (1–3)-[Beta]-D-glucan synthase activity. J Antibiot 41:697–701

    Article  CAS  Google Scholar 

  • Takeshima H, Inokoshi J, Takada Y, Tanaka H, Omura S (1989) A deacylation enzyme for aculeacin A, a neutral lipopeptide antibiotic, from Actinoplanes utahensis: purification and characterization. J Biochem 105:606–610

    CAS  Google Scholar 

  • Tang J, Parr TR (1991) W-1 solubilization and kinetics of inhibition by cilofungin of Candida albicans (1,3)-[Beta]-glucan synthase. Antimicrob Agents Chemother 35:99–103

    Article  CAS  Google Scholar 

  • Tkacz JS, Giacobbe RA, Monaghan RL (1993) Improvement in the titer of echinocandin-type antibiotics: a magnesium-limited medium supporting the biphasic production of pneumocandins A0 and B0. J Ind Microbiol 11:95–103

    Article  CAS  Google Scholar 

  • Torres-Bacete J, Hormigo D, Stuart M, Arroyo M, Torres P, Castillón MP, Acebal C, García JL, de la Mata I (2007) Newly discovered penicillin acylase activity of aculeacin A acylase from Actinoplanes utahensis. Appl Environ Microbiol 73:5378–5381

    Article  CAS  Google Scholar 

  • Tóth V (2012) Characterization of Aspergillus nidulans var. roseus ATCC 58397, investigation its echinocandin B and sterigmatocystin production. Dissertation, University of Debrecen

  • Tóth V, CsT N, Miskei M, Pócsi I, Emri T (2011) Polyphasic characterization of “Aspergillus nidulans var. roseus” ATCC 58397. Folia Microbiol 56:381–388

    Article  CAS  Google Scholar 

  • Tóth V, CsT N, Pócsi I, Emri T (2012) The echinocandin B producer fungus Aspergillus nidulans var. roseus ATCC 58397 does not possess innate resistance against its lipopeptide antimycotic. Appl Microbiol Biotechnol 95:113–122

    Article  CAS  Google Scholar 

  • Traber R, Keller-Juslén C, Loosli HR, Kuhn M, Von Wartburg A (1979) Cyclopeptid-Antibiotika aus Aspergillus-Arten. Struktur der Echinocandine C und D. Helv Chim Acta 62:1252–1267

    Article  CAS  Google Scholar 

  • Tscherter H, Dreyfuss MM (1982) New metabolites. Processes for their production and their use. Internat. Patent Appl PCT/EP8/00121

  • Ueda S, Sakamoto K, Oohata N, Tsuboi M, Yamashita M, Hino M, Yamada M, Hashimoto S (2010) Screening and characterization of microorganisms with FR901379 acylase activity. J Antibiot 63:65–70

    Article  CAS  Google Scholar 

  • Ueda S, Kinoshita M, Tanaka F, Tsuboi M, Shimizu S, Oohata N, Hino M, Yamada M, Isogai Y, Hashimoto S (2011a) Strain selection and scale-up fermentation for FR901379 acylase production by Streptomyces sp. no. 6907. J Biosci Bioeng 112:409–414

    Article  CAS  Google Scholar 

  • Ueda S, Shibata T, Ito K, Oohata N, Yamashita M, Hino M, Yamada M, Isogai Y, Hashimoto S (2011b) Cloning and expression of the FR901379 acylase gene from Streptomyces sp. no. 6907. J Antibiot 64:169–175

    Article  CAS  Google Scholar 

  • van de Sande WW, Fahal AH, Bakker-Woudenberg IA, van Belkum A (2010) Madurella mycetomatis is not susceptible to the echinocandin class of antifungal agents. Antimicrob Agents Chemother 54:2738–2740

    Article  CAS  Google Scholar 

  • van Duin D, Casadevall A, Nosanchuk JD (2002) Melanization of Cryptococcus neoformans and Histoplasma capsulatum reduces their susceptibilities to amphotericin B and caspofungin. Antimicrob Agents Chemother 46:3394–3400

    Article  CAS  Google Scholar 

  • Vazquez JA, Lynch M, Sobel JD (1995) In vitro activity of a new pneumocandin antifungal agent, L-733,560 against azole-susceptible and -resistant Candida and Torulopsis species. Antimicrob Agents Chemother 39:2689–2691

    Article  CAS  Google Scholar 

  • Verwer PE, van Duijn ML, Tavakol M, Bakker-Woudenberg IA, van de Sande WW (2012) Reshuffling of Aspergillus fumigatus cell wall components chitin and β-glucan under the influence of caspofungin or nikkomycin Z alone or in combination. Antimicrob Agents Chemother 56:1595–1598

    Article  CAS  Google Scholar 

  • Walker LA, Munro CA, de Bruijn I, Lenardon MD, McKinnon A, Gow NA (2008) Stimulation of chitin synthesis rescues Candida albicans from echinocandins. PLoS Pathog 4(4):e1000040

    Article  CAS  Google Scholar 

  • Walker LA, Gow NAR, Munro CA (2010) Fungal echinocandin resistance. Fungal Genet Biol 47:117–126

    Article  CAS  Google Scholar 

  • Walker LA, Gow NA, Munro CA (2012) Elevated chitin content reduces the susceptibility of Candida species to caspofungin. Antimicrob Agents Chemother. doi:10.1128/AAC.01486-12

  • Wiederhold NP (2007) Attenuation of echinocandin activity at elevated concentrations: a review of the paradoxical effect. Curr Opin Infect Dis 20:574–578

    Google Scholar 

  • Wittmann M, Linne U, Pohlmann V, Marahiel MA (2008) Role of DptE and DptF in the lipidation reaction of daptomycin. FEBS J 275:5343–5354

    Article  CAS  Google Scholar 

  • Yamaguchi H, Hiratani T, Iwata K, Yamamoto Y (1982) Studies on the mechanism of antifungal action of aculeacin A. J Antibiot 35:210–219

    Article  CAS  Google Scholar 

  • Yamaguchi H, Hiratani T, Baba MN, Osumi M (1985) Effect of aculeacin A, a wall-active antibiotic, on synthesis of the yeast cell wall. Microbiol Immunol 29:609–623

    CAS  Google Scholar 

  • Yao J, Liu H, Zhou T, Chen H, Miao Z, Sheng C, Zhang W (2012) Total synthesis and structure–activity relationships of new echinocandin-like antifungal cyclolipohexapeptides. Eur J Med Chem 50:196–208

    Article  CAS  Google Scholar 

  • Youssar L, Grüning BA, Erxleben A, Günther S, Hüttel W (2012) Genome sequence of the fungus Glarea lozoyensis: the first genome sequence of a species from the Helotiaceae family. Eukaryot Cell 11:250, Erratum in: Eukaryot Cell 11:829

    Article  CAS  Google Scholar 

  • Zambias RA, Hammond ML, Heck JV, Bartizal K, Trainor C, Abruzzo G, Schmatz DM, Nollstadt KM (1992) Preparation and structure relationships of simplified analogues of the antifungal agent cilofungin: a total synthesis approach. J Med Chem 35:2843–2855

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the TAMOP 4.2.1/B-09/1/KONV-2010-0007, TAMOP-4.2.2/B-10/1-2010-0024 and TÁMOP-4.2.2.A-11/1/KONV-2012-0045 projects and was implemented through the New Hungary Development Plan, co-financed by the European Union and the European Social Fund.

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Emri, T., Majoros, L., Tóth, V. et al. Echinocandins: production and applications. Appl Microbiol Biotechnol 97, 3267–3284 (2013). https://doi.org/10.1007/s00253-013-4761-9

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