Introduction. Sporotrichosis, caused by species of the Sporothrix schenckii complex, is the most prevalent subcutaneous mycosis in many areas of Latin America. Statins are a class of drugs widely used for lowering high sterol levels through their action on 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in the synthesis of sterol.
Aim. In this study, the antifungal activity of statins (simvastatin, atorvastatin, pravastatin) against planktonic cells and biofilms of S. schenckii complex species was evaluated, as well as the interaction of pravastatin with classical antifungals (amphotericin B, itraconazole, terbinafine).
Methodology. Eighteen strains of Sporothrix species were used. The antifungal susceptibility assay was performed using the broth microdilution method. Mature biofilms were exposed to statins and metabolic activity was measured by the XTT reduction assay.
Results. MICs of statins ranged from 8 to 512 μg ml−1 and from 8 to 256 μg ml−1 for filamentous and yeast forms, respectively. Regarding mature biofilms, MICs of 50 % inhibition (SMIC50) were 128 μg ml−1 for simvastatin and atorvastatin and >2048 μg ml−1 for pravastatin. MICs of 90 % inhibition (SMIC90) were 512 μg ml−1 for simvastatin and >2048 μg ml−1 for atorvastatin and pravastatin.
Conclusion. These results highlight the antifungal and antibiofilm potential of statins against S. schenckii complex species.
BrilhanteRSN,
de AguiarFRM,
da SilvaMLQ,
de OliveiraJS,
de CamargoZP et al. Antifungal susceptibility of Sporothrix schenckii complex biofilms. Med Mycol2018; 56:297–306 [View Article][PubMed]
MitchellKF,
ZarnowskiR,
AndesDR.
Fungal super glue: the biofilm matrix and its composition, assembly, and functions. PLoS Pathog2016; 12:e1005828 [View Article][PubMed]
BrilhanteRSN,
SilvaMLQda,
PereiraVS,
de OliveiraJS,
MacielJM et al. Potassium iodide and miltefosine inhibit biofilms of Sporothrix schenckii species complex in yeast and filamentous forms. Med Mycol2019; 57:764–772 [View Article][PubMed]
Borba-SantosLP,
Reis de SáLF,
RamosJA,
RodriguesAM,
de CamargoZP et al. Tacrolimus Increases the Effectiveness of Itraconazole and Fluconazole against Sporothrix spp. Front Microbiol2017; 8:8 [View Article][PubMed]
NyilasiI,
KocsubéS,
KrizsánK,
GalgóczyL,
PappT et al. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Sabouraudia2013; 52:140–148
ZhouY,
YangH,
ZhouX,
LuoH,
TangF et al. Lovastatin synergizes with itraconazole against planktonic cells and biofilms of Candida albicans through the regulation on ergosterol biosynthesis pathway. Appl Microbiol Biotechnol2018; 102:5255–5264 [View Article][PubMed]
CLSIReference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts; Approved Standard - Third Edition. CLSI document M27A3 Wayne, PA: Clinical and Laboratory Standards; 2008
Almeida-PaesR,
Brito-SantosF,
Figueiredo-CarvalhoMHG,
MachadoACS,
OliveiraMME et al. Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis
. Mem Inst Oswaldo Cruz2017; 112:376–381 [View Article][PubMed]
ValentínA,
CantónE,
PemánJ,
Fernandez-RiveroME,
Tormo-MasMA et al. In vitro activity of anidulafungin in combination with amphotericin B or voriconazole against biofilms of five Candida species. J Antimicrob Chemother2016; 71:3449–3452 [View Article][PubMed]
RodriguesAM,
de HoogGS,
de CamargoZP.
Sporothrix species causing outbreaks in animals and humans driven by Animal-Animal transmission. PLoS Pathog2016; 12:e1005638 [View Article][PubMed]
Borba-SantosLP,
RodriguesAM,
GaginiTB,
FernandesGF,
CastroR et al. Susceptibility of Sporothrix brasiliensis isolates to amphotericin B, azoles, and terbinafine. Med Mycol2015; 53:178–188 [View Article][PubMed]
SanchoteneKO,
BrandoltTM,
KlafkeGB,
PoesterVR,
XavierMO.
In vitro susceptibility of Sporothrix brasiliensis: Comparison of yeast and mycelial phases. Med Mycol20171–8
HoffmanWF,
AlbertsAW,
AndersonPS,
ChenJS,
SmithRL et al. 3-Hydroxy-3-Methylglutaryl-Coenzyme A reductase inhibitors. 4. side chain ester derivatives of mevinolin. J Med Chem1986; 29:849–852 [View Article][PubMed]
GrazianoTS,
CuzzullinMC,
FrancoGC,
Schwartz-FilhoHO,
de AndradeED et al. Statins and antimicrobial effects: simvastatin as a potential drug against Staphylococcus aureus biofilm. PLoS One 10:e0128098 [View Article]
GyetvaiA,
EmriT,
TakácsK,
DergezT,
FeketeA et al. Lovastatin possesses a fungistatic effect against Candida albicans, but does not trigger apoptosis in this opportunistic human pathogen. FEMS Yeast Res2006; 6:1140–1148 [View Article][PubMed]
NyilasiI,
KocsubéS,
KrizsánK,
GalgóczyL,
PappT et al. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Med Mycol2013; 52:140–148