Year: 2019
Type: dissertation
Abstract: Fungal pathogens of humans cause harmful infections and can cause diverse diseases in humans \nwhich range from superficial skin infections to life-threatening diseases. The opportunistic \npathogen Candida albicans causes a wide range of diseases primarily in immunocompromised \nindividuals. Aspergillus fumigatus is a serious cause of disease in immune deficient patients or in \nthose with pulmonary disease (e.g. cystic fibrosis (CF), asthma), and is the second most common \nopportunistic fungal pathogen of humans. Galleria mellonella larvae are an ideal model of \ninfection to quickly and easily evaluate the virulence of a range of human fungal pathogens. \nAtorvastatin is a member of the statin drug family which are the main therapeutic agents used to \ndecrease high serum cholesterol levels by inhibiting HMG-CoA reductase enzyme. HMG-CoA is \nan enzyme that is responsible for the production of farnesyl diphosphate which is the precursor for \nthe production of cholesterol in humans and ergosterol in fungi. The aim of the work presented \nhere was to analyse the antifungal activity of a widely prescribed statin (atorvastatin) and assess \nthe effect of atorvastatin on the on the virulence of C. albicans and A. fumigatus. The study also \ninvestigated the effect of atorvastatin on G. mellonella larvae. The results obtained demonstrated \nthat atorvastatin has anti-fungal activity and it reduced growth and viability of C. albicans and A. \nfumigatus. Exposure of C. albicans and A. fumigatus to this drug leads to the release of protein, \namino acids and a reduction in ergosterol synthesis, and increased gliotoxin release in A. fumigatus. \nProteomic analysis revealed increased abundance of proteins associated with an oxidative stress \nresponse, ergosterol biosynthesis and secondary metabolites. Atorvastatin can be used to inhibit \nthe growth of C. albicans and A. fumigatus in G. mellonella larvae. Atorvastatin was shown to be \nnon-toxic to G. mellonella larvae and not to induce an immune response when administered to \nlarvae. The results presented in this thesis indicate that atorvastatin is non-toxic and capable of inhibiting the growth and virulence of C. albicans and A. fumigatus.
Author: Bashir Ajdidi, Ahmad
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7026783736