Bashir Ajdidi, Ahmad (2019) Analysis of the effect of atorvastatin on the virulence of Fungal Pathogens. PhD thesis, National University of Ireland Maynooth.
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Abstract
Fungal pathogens of humans cause harmful infections and can cause diverse diseases in humans
which range from superficial skin infections to life-threatening diseases. The opportunistic
pathogen Candida albicans causes a wide range of diseases primarily in immunocompromised
individuals. Aspergillus fumigatus is a serious cause of disease in immune deficient patients or in
those with pulmonary disease (e.g. cystic fibrosis (CF), asthma), and is the second most common
opportunistic fungal pathogen of humans. Galleria mellonella larvae are an ideal model of
infection to quickly and easily evaluate the virulence of a range of human fungal pathogens.
Atorvastatin is a member of the statin drug family which are the main therapeutic agents used to
decrease high serum cholesterol levels by inhibiting HMG-CoA reductase enzyme. HMG-CoA is
an enzyme that is responsible for the production of farnesyl diphosphate which is the precursor for
the production of cholesterol in humans and ergosterol in fungi. The aim of the work presented
here was to analyse the antifungal activity of a widely prescribed statin (atorvastatin) and assess
the effect of atorvastatin on the on the virulence of C. albicans and A. fumigatus. The study also
investigated the effect of atorvastatin on G. mellonella larvae. The results obtained demonstrated
that atorvastatin has anti-fungal activity and it reduced growth and viability of C. albicans and A.
fumigatus. Exposure of C. albicans and A. fumigatus to this drug leads to the release of protein,
amino acids and a reduction in ergosterol synthesis, and increased gliotoxin release in A. fumigatus.
Proteomic analysis revealed increased abundance of proteins associated with an oxidative stress
response, ergosterol biosynthesis and secondary metabolites. Atorvastatin can be used to inhibit
the growth of C. albicans and A. fumigatus in G. mellonella larvae. Atorvastatin was shown to be
non-toxic to G. mellonella larvae and not to induce an immune response when administered to
larvae. 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.
Item Type: | Thesis (PhD) |
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Keywords: | Analysis; effect; atorvastatin; virulence; Fungal Pathogens; |
Academic Unit: | Faculty of Science and Engineering > Biology |
Item ID: | 13612 |
Depositing User: | IR eTheses |
Date Deposited: | 17 Nov 2020 15:08 |
URI: | https://mural.maynoothuniversity.ie/id/eprint/13612 |
Use Licence: | This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here |
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