(228fi) Antibacterial Activity of Catechins Against Aggregatibacter Actinomycetemcomitans

Antibacterial
Activity of Catechins against Aggregatibacter actinomycetemcomitans

Virulence
factors are molecules produced by pathogenic bacteria that allow them to
establish a niche within the host.  These molecules include adhesions,
enzymes, and toxins, among many others.  Our lab is focused on inhibiting
the action of toxins for the development of antivirulence strategies to treat
bacterial infections.  The gram-negative bacterium Aggregatibacter
actinomycetemcomitans (A.a.) produces numerous virulence factors,
including a leukotoxin (LtxA), which selectively kills host immune cells. It
has been reported that catechins, polyphenols extracted from green tea leaves,
have antibacterial properties against A.a. However, the mechanism by
which catechins interact with both the bacteria and mammalian cells has not yet
been uncovered. In this project, six common catechins were used: (-) catechin
(C), epicatechin (EC), epigallocatechin (EGC), gallocatechin gallate (GCg),
epigallocatechin gallate (EGCg) and epicatechin gallate (ECg) to correlate
inhibition of LtxA activity with the catechins¡¯ ability to alter the host
membrane properties.  In addition, the effect of the six catechins on
bacterial membrane properties was examined. Our results indicate that the
galloylated catechins significantly alter membrane fluidity in both model
membranes and target cell (THP-1) membranes, while non-galloyated catechins
have little effect on membrane fluidity.  These changes appear to be
caused by the catechins alone, as there are no changes in the cell membrane
cholesterol composition after incubation with the catechins.  Two of these
galloyated catechins, EGCg and GCg, inhibit the ability of LtxA to kill target
cells, while the non-galloylated catechins do not, suggesting that the ability
of the catechins to alter target cell membrane fluidity plays a role in their
inhibition of toxin activity.  Our current work is focused on better
understanding this relationship as well as investigating the effects of the
catechins on bacterial cell membrane properties to better define their
antibacterial properties.