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.
