Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species

Abstract

The antifungal activity of some statins against different fungal species has been reported. Thus, at the first moment, the in vitro antifungal activity of simvastatin, atorvastatin and pravastatin was tested against Candida spp. and Cryptococcus spp. Then, in a second approach, considering that the best results were obtained for simvastatin, this drug was evaluated in combination with antifungal drugs against planktonic growth and tested against biofilms of Candida spp. and Cryptococcus spp. Drug susceptibility testing was performed using the microdilution broth method, as described by the Clinical and Laboratory Standards Institute. The interaction between simvastatin and antifungals against planktonic cells was analyzed by calculating the fractional inhibitory concentration index. Regarding biofilm susceptibility, simvastatin was tested against growing biofilm and mature biofilm of one strain of each tested yeast species. Simvastatin showed inhibitory effect against Candida spp. and Cryptococcus spp. with minimum inhibitory concentration values ranging from 15.6 to 1000 mg L(-1) and from 62.5 to 1000 mg L(-1), respectively. The combination of simvastatin with itraconazole and fluconazole showed synergism against Candida spp. and Cryptococcus spp., while the combination of simvastatin with amphotericin B was synergistic only against Cryptococcus spp. Concerning the biofilm assays, simvastatin was able to inhibit both growing biofilm and mature biofilm of Candida spp. and Cryptococcus spp. The present study showed that simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species.

Anticandidal effect of endophytic bacteria isolated from Equisetum arvense L. against Candida albicans and Candida glabrata

“…The occurrence of persistent fungal infections is mainly caused by opportunistic fungi of the genus Candida 1 . More than 17 diverse Candida species are well-known etiological agents of human illness, while more than 90% of persistent infections are caused by C. albicans and C. glabrata [2][3][4] .…”

Darunavir inhibits Cryptococcus neoformans/Cryptococcus gattii species complex growth and increases the susceptibility of biofilms to antifungal drugs

“…Biofilm formation was assessed based on the method described by Brilhante et al [16], with modifications. Fungal inocula were prepared in RPMI 1640 medium at a concentration of 1×10 6 c.f.u.…”

In vitro inhibitory effect of statins on planktonic cells and biofilms of the Sporothrix schenckii species complex

“…Statin stock solutions were prepared at a concentration of 10 000 µg ml −1 . Simvastatin (Medley Pharmaceutical) was activated by hydrolysis in ethanolic NaOH [15 % (v/v) ethanol, 0.25 % (w/v) NaOH] at 60 °C for 1 h. Atorvastatin (Medley Pharmaceutical) was diluted in DMSO and pravastatin (Medley Pharmaceutical) was diluted in sterile distilled water [10]. Amphotericin B (Sigma-Aldrich), itraconazole (Janssen Pharmaceutica) and terbinafine (Sigma-Aldrich) were prepared according to the document M38-A2 [12].…”

“…Susceptibility tests were performed in 96-well microplates using the broth microdilution method according to the documents M38-A2 (filamentous form) and M27-A3 (yeast form) [12,13], with adaptations. The drug concentrations tested ranged from 4 to 2048 μg ml −1 (filamentous form) and from 0.125 to 64 μg ml −1 (yeast form) for simvastatin; from 4 to 2048 μg ml −1 for pravastatin (filamentous and yeast forms); from 1 to 512 μg ml −1 for atorvastatin (filamentous and yeast forms) [10]; and from 0.03 to 16 μg ml −1 for amphotericin B, itraconazole and terbinafine (filamentous and yeast forms). Inocula were prepared in a 0.9 % saline solution and then adjusted to a final concentration of 0.4-5×10 4 c.f.u.…”

“…The most commonly used drugs for sporotrichosis treatment are potassium iodide, itraconazole, terbinafine and amphotericin B [7]. However, the high toxicity of amphotericin B and the limited number of drugs for the treatment of sporotrichosis have encouraged the investigation for repositioning of drugs having antifungal activity [8], such as statins, which have in vitro antifungal activity against yeasts and filamentous fungi [9][10][11]. However, the activity of these drugs against dimorphic fungi, such as those belonging to the S. schenckii species complex, is not yet known.…”