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Title: Epigallocatechin gallate inhibits leukotoxin release by Aggregatibacter actinomycetemcomitans by promoting association with the bacterial membrane
Abstract

The oral pathogen,Aggregatibacter actinomycetemcomitans, produces a number of virulence factors, including a leukotoxin (LtxA), which specifically kills human white blood cells, to provide a colonization advantage to the bacterium. Strains ofA. actinomycetemcomitansthat produce more LtxA have been more closely linked to disease, indicating that this toxin plays a key role in pathogenesis of the bacterium. Disruption of the activity of LtxA thus represents a promising approach to reducing the pathogenicity of the bacterium. Catechins are polyphenolic molecules derived from plants, which have shown potent antibacterial and antitoxin activities. We have previously shown that galloylated catechins are able to prevent LtxA delivery to host cells by altering the toxin's secondary structure and preventing binding to cholesterol on the host cell membrane. Here, we have investigated how one particular galloylated catechin, epigallocatechin gallate (EGCg), affectsA. actinomycetemcomitansgrowth and toxin secretion. Our results demonstrate that EGCg, at micromolar concentrations, inhibitsA. actinomycetemcomitansgrowth, as has been reported for other bacterial species. At subinhibitory concentrations, EGCg promotes LtxA production, but the toxicity of the bacterial supernatant against human immune cells is reduced. The results of our biophysical studies indicate that this seemingly contradictory result is caused by an EGCg‐mediated enhancement of LtxA affinity for the bacterial cell surface. Together, these results demonstrate the potential of EGCg in the treatment of virulentA. actinomycetemcomitansinfections.

 
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NSF-PAR ID:
10458719
Author(s) / Creator(s):
 ;  ;  ;  ;  
Publisher / Repository:
Wiley-Blackwell
Date Published:
Journal Name:
Molecular Oral Microbiology
Volume:
35
Issue:
1
ISSN:
2041-1006
Page Range / eLocation ID:
p. 29-39
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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