Inhibition of α-hemolysin activity of Staphylococcus aureus by theaflavin 3,3’-digallate

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A. Goc, W. Sumera, M. Rath, A. Niedzwiecki

PLoS ONE 18(8): e0290904.

The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era.

Here, we set out to examine mechanisms by which theaflavin 3,3’-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacterio-static and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion. A supportive SPR assay reinforced these results and further revealed binding of TF3 to Hla with KD = 4.57×10−5 M. Interestingly, TF3 was also able to protect human primary keratino-cytes from Hla-induced cell death, being at the same time non-toxic for them. Further analy-sis of TF3 properties revealed that TF3 blocked Hla-prompting immune reaction by inhibiting production and secretion of IL1β, IL6, and TNFα in vitro and in vivo, through affect-ing NFκB activity. Additionally, we observed that TF3 also markedly attenuated S. aureus-induced barrier disruption, by inhibiting Hla-triggered E-cadherin and ZO-1 impairment. Overall, by blocking activity of Hla, TF3 subsequently subdued the inflammation and pro-tected the epithelial barrier, which is considered as beneficial to relieving skin injury.

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