Biological consequences of statins in Candida species and possible implications for human health.
The statins, simvastatin and atorvastatin are the most widely prescribed drugs. Statins lower cholesterol levels through their action on HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, an essential enzyme for the biosynthesis of cholesterol. Fungal HMG-CoA reductases are also inhibited by statins, resulting in reduced levels of ergosterol (the fungal equivalent of cholesterol) and concomitant growth inhibition. This effect occurs in a range of fungal species and possibly affects fungal colonization of people on statin therapy. Furthermore, it may suggest that statins could have a role in new antifungal therapies. Possibly associated with the reduction in ergosterol levels, statins also inhibit respiratory growth. In the yeast, Candida glabrata, passage with statins dramatically increased the frequencies of petite mutants that were devoid of mitochondrial DNA, suggesting that statins caused a defect in the maintenance of mitochondrial DNA. These observations in C. glabrata may provide further insights into side effects of statins in humans undergoing treatment for hypercholesterolaemia. In addition, C. glabrata may be highly useful for the preliminary screening of agents to reduce statin side effects.
Wikhe
K
K
CSIRO (Commonwealth Scientific and Industrial Research Organisation) Health and Molecular and Technologies and P-Health Flagship, 343 Royal Parade, Parkville, VIC 3052, Australia.
Westermeyer
C
C
Macreadie
I G
IG
D000935:Antifungal Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D041221:Candida glabrata / Q000145:classification* / Q000187:drug effects* / Q000254:growth & development; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*
D000935:Antifungal Agents; D004272:DNA, Mitochondrial; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases