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Volume 59, Issue 2

interactions between primycin and different statins in their effects against some clinically important fungi Free

Abstract

The antifungal activities of primycin (PN) and various statins against some opportunistic pathogenic fungi were investigated. PN completely inhibited the growth of (MIC 64 μg ml) and (MIC 32 μg ml), and was very effective against (MIC 2 μg ml), but had little effect on , or (MICs >64 μg ml). The fungi exhibited different degrees of sensitivity to the statins; fluvastatin (FLV) and simvastatin (SIM) exerted potent antifungal activities against a wide variety of clinically important fungal pathogens. Atorvastatin, rosuvastatin and lovastatin (LOV) had a slight effect against all fungal isolates tested, whereas pravastatin was completely ineffective. The interactions between PN and the different statins were investigated using a standard chequerboard titration method. When PN was combined with FLV, LOV or SIM, both synergistic and additive effects were observed. The extent of inhibition was higher when these compounds were applied together, and the concentrations of PN and the given statin needed to block fungal growth completely could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities was investigated.

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Keyword(s): ATO, atorvastatin , FIC, fractional inhibitory concentration , FLV, fluvastatin , IR, interaction ratio , LOV, lovastatin , PN, primycin , PRA, pravastatin , ROS, rosuvastatin and SIM, simvastatin
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2010-02-01
2024-04-28
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References

  1. Afeltra J., Verweij P. E. 2003; Antifungal activity of nonantifungal drugs. Eur J Clin Microbiol Infect Dis 22:397–407 [CrossRef]
     [Google Scholar]
  2. Blaskó K., Györgyi S., Horváth I. 1979; Effect of primycin on monovalent cation transport of erythrocyte membrane and lipid bilayer. J Antibiot 32:408–413 [CrossRef]
     [Google Scholar]
  3. Chamilos G., Lewis R. E., Kontoyiannis D. P. 2006; Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob Agents Chemother 50:96–103 [CrossRef]
     [Google Scholar]
  4. Chin N. X., Weitzman I., Della-Latta P. 1997; In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with fluconazole and itraconazole against Candida species and Cryptococcus neoformans . Antimicrob Agents Chemother 41:850–852
     [Google Scholar]
  5. Cordle A., Koenigsknecht-Talboo J., Wilkinson B., Limpert A., Landreth G. 2005; Mechanism of statin-mediated inhibition of small G-protein function. J Biol Chem 280:34202–34209 [CrossRef]
     [Google Scholar]
  6. Galgóczy L., Papp T., Lukács Gy., Leiter É., Pócsi I., Vágvölgyi Cs. 2007; Interactions between statins and Penicillium chrysogenum antifungal protein (PAF) to inhibit the germination of sporangiospores of different sensitive Zygomycetes . FEMS Microbiol Lett 270:109–115 [CrossRef]
     [Google Scholar]
  7. Galgóczy L., Kovács L., Krizsán K., Papp T., Vágvölgyi Cs. 2009a; Inhibitory effects of cysteine and cysteine derivatives on germination of sporangiospores and hyphal growth of different Zygomycetes. Mycopathologia 168:125–134 [CrossRef]
     [Google Scholar]
  8. Galgóczy L., Nyilasi I., Papp T., Vágvölgyi Cs. 2009b; Are statins applicable for the prevention and treatment of zygomycosis?. Clin Infect Dis 49:483–484 [CrossRef]
     [Google Scholar]
  9. Gisi U. 1996; Synergistic interaction of fungicides in mixtures. Phytopathology 86:1273–1279
     [Google Scholar]
  10. Gyetvai Á., Emri T., Takács K., Dergez T., Fekete A., Pesti M., Pócsi I., Lenkey B. 2006; Lovastatin possesses a fungistatic effect against Candida albicans but does not trigger apoptosis in this opportunistic human pathogen. FEMS Yeast Res 6:1140–1148 [CrossRef]
     [Google Scholar]
  11. Henderson F., Marshall I. G. 1984; The effects of the antibiotic, primycin, on spontaneous transmitter release at the neuromuscular junction. Br J Pharmacol 81:61–67 [CrossRef]
     [Google Scholar]
  12. Horvath I., Kramer M., Bauer P. I., Buki K. G. 1979; The mode of action of primycin. Arch Microbiol 121:135–139 [CrossRef]
     [Google Scholar]
  13. Kontoyiannis D. P. 2007; Decrease in the number of reported cases of zygomycosis among patients with diabetes mellitus: a hypothesis. Clin Infect Dis 44:1089–1090 [CrossRef]
     [Google Scholar]
  14. Liao J. K., Laufs U. 2005; Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118 [CrossRef]
     [Google Scholar]
  15. Lorenz R. T., Parks L. W. 1990; Effects of lovastatin (mevinolin) on sterol levels and on activity of azoles in Saccharomyces cerevisiae . Antimicrob Agents Chemother 34:1660–1665 [CrossRef]
     [Google Scholar]
  16. Lukács Gy., Papp T., Nyilasi I., Nagy E., Vágvölgyi Cs. 2004; Differentiation of Rhizomucor species on the basis of their different sensitivities to lovastatin. J Clin Microbiol 42:5400–5402 [CrossRef]
     [Google Scholar]
  17. Macreadie I. G., Johnson G., Schlosser T., Macreadie P. I. 2006; Growth inhibition of Candida species and Aspergillus fumigatus by statins. FEMS Microbiol Lett 262:9–13 [CrossRef]
     [Google Scholar]
  18. Meszaros L., Hoffmann L., Paroczai M., Konig T., Horvath I. 1980; Depletion of Mg2+ and permeability increase of the mitochondrial inner membrane by primycin. J Antibiot 33:523–524 [CrossRef]
     [Google Scholar]
  19. Miida T., Hirayama S., Nakamura Y. 2004; Cholesterol-independent effects of statins and new therapeutic strategies: ischemic stroke and dementia. J Atheroscler Thromb 11:253–264 [CrossRef]
     [Google Scholar]
  20. Natesan S. K., Chandrasekar P. H., Alangaden G. J., Manavathu E. K. 2008; Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus in vitro. Diagn Microbiol Infect Dis 60:369–373 [CrossRef]
     [Google Scholar]
  21. NCCLS 1997 Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts , approved standard, document M27-A Wayne, PA: National Committee for Clinical Laboratory Standards;
     [Google Scholar]
  22. NCCLS 2002 Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi , approved standard, document M38-A Wayne, PA: National Committee for Clinical Laboratory Standards;
     [Google Scholar]
  23. Nucci M. 2003; Emerging moulds: Fusarium , Scedosporium and Zygomycetes in transplant recipients. Curr Opin Infect Dis 16:607–612 [CrossRef]
     [Google Scholar]
  24. Roze L. V., Linz J. E. 1998; Lovastatin triggers an apoptosis-like cell death process in the fungus Mucor racemosus . Fungal Genet Biol 25:119–133 [CrossRef]
     [Google Scholar]
  25. Schachter M. 2005; Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 19:117–125 [CrossRef]
     [Google Scholar]
  26. Singh N. 2001; Trends in the epidemiology of opportunistic fungal infections: predisposing factors and the impact of antimicrobial use practices. Clin Infect Dis 33:1692–1696 [CrossRef]
     [Google Scholar]
  27. Sun H.-Y., Singh N. 2009; Antimicrobial and immunomodulatory attributes of statins: relevance in solid-organ transplant recipients. Clin Infect Dis 48:745–755 [CrossRef]
     [Google Scholar]
  28. Szabo A. Z., Gaal J., Marmarosi K., Sebestyen G., Miholics G., Kovacs M. 1993; Pharmaceutical compositions containing primycin. Patent EP0347225
     [Google Scholar]
  29. Uri J. V., Actor P. 1979; Crystallization and antifungal activity of primycin. J Antibiot 32:1207–1209 [CrossRef]
     [Google Scholar]
  30. Vályi-Nagy T., Uri J., Szilágyi I. 1954; Primycin, a new antibiotic. Nature 174:1105–1106
     [Google Scholar]
  31. Walsh T. J., Groll A. H. 1999; Emerging fungal pathogens: evolving challenges to immunocompromised patients for the twenty-first century. Transpl Infect Dis 1:247–261 [CrossRef]
     [Google Scholar]
  32. Walsh T. J., Groll A., Hiemenz J., Fleming R., Roilides E., Anaissie E. 2004; Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect 10 (Suppl. 1):48–66 [CrossRef]
     [Google Scholar]
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In vitro interactions between primycin and different statins in their effects against some clinically important fungi
J. Med. Microbiol. 59, 200 (2010); https://doi.org/10.1099/jmm.0.013946-0
/content/journal/jmm/10.1099/jmm.0.013946-0
/content/journal/jmm/10.1099/jmm.0.013946-0
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