The Effect of Curcumin on Francisella and FtsZ
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Authors
Bobde, Shravani
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Abstract
This thesis assesses the effect of curcumin on Francisella (F.) novicida and the protein FtsZ. Curcumin is a polyphenolic compound found in turmeric that is widely used as a spice and an ayurvedic medicine in South-East Asia. F. novicida is the non-virulent strain of F. tularensis and is commonly used as a model organism as it can be used in a BSL2 laboratory. Antibacterial assays demonstrated that curcumin inhibited bacterial growth at 16 μg/ml (Minimal Inhibitory Concentration) and did not affect biofilm formation in F. novicida. Curcumin showed a dose-dependent relationship in significantly reducing bacterial load in F. novicida-infected mouse macrophages, suggesting that curcumin is able to enter the macrophages and inhibit bacterial growth. – Curcumin showed synergy with three antibiotics doxycycline, erythromycin and ciprofloxacin, suggesting that a combined approach to therapy might be advantageous in treating tularemia. Because of the role of FtsZ in regulating cell division through its interaction with minC, minD, and minE, we examined whether curcumin treatment may alter Francisella morphology, or cause filamentation, as is reported for Bacillus. Curcumin treatment did not show significant changes in bacterial morphology or size but showed an increase in granularity as measured by Fluorescent Activated Cell Sorting. Bioinformatics analysis of curcumin and FtsZ interaction was modeled for the F. novicida protein, and showed a similar docking site with GTP as reported for E. coli FtsZ. A consensus of residues 138 and 142 as being involved in GTP binding was observed using multiple software confirming that curcumin and GTP bind at the same site in FtsZ. Targeting FtsZ with Curcumin provide novel potential target to treat this bacterial infection; however, low bioavailability of curcumin poses a challenge in using curcumin as a therapeutic.
Description
This thesis has been embargoed for 1 year and will not be available until December 2018 at the earliest.
Keywords
Francisella, Curcumin, Inhibition, FtsZ