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 of A. actinomycetemcomitans that 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), affects A. actinomycetemcomitans growth and toxin secretion. Our results demonstrate that EGCg, at micromolar concentrations, inhibits A. actinomycetemcomitans growth, 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 virulent A. actinomycetemcomitans infections.

Prevalence of JP2 and Non-JP2 Genotypes of Aggregatibacter actinomycetemcomitans and Oral Hygiene Practice of Kenyan Adolescents in Maasai Mara

“…For example, plant materials may contain beneficial plant extracts that exert an anti-leukotoxic potential [ 32 , 33 , 34 , 35 ]. Recently, proanthocyanidins and epigallocatechin gallate of plant origin have been found to neutralize the effect of the A. actinomycetemcomitans leukotoxin [ 35 , 36 , 37 ].…”

Applications of Catechins in the Treatment of Bacterial Infections

“…We also observed that EGCg has large effects on LtxA release. When A. actinomycetemcomitans was treated with EGCg at a sub-inhibitory concentration (5 μg/mL), more LtxA was produced; however, most of the toxin remained in association with the bacterial cell surface rather than being secreted into the supernatant [ 44 , 45 ].…”

Interactions of Tea-Derived Catechin Gallates with Bacterial Pathogens

“…The secondary structure of the toxin was dramatically altered in the presence of catechin gallates and resulted in inhibition of toxin binding to cholesterol, an important initial step in the cytotoxic mechanism. EGCg also reduces secretion of the toxin due to EGCg-mediated enhancement of LtxA affinity for the bacterial cell surface [71]. EGCg supressed the proliferation of vegetative B. cereus and B. subtilis but not the germination of spores of these bacteria [72].…”