Investigation of the inhibitory effect and mechanism of EGCG against Streptococcus suis sortase A.

Abstract

Streptococcus suis (S. suis) seriously harms people and animals, and importantly, causes great economic losses in the pig industry. Similar to most gram-positive pathogenic bacteria, sortase A (SrtA) of S. suis can mediate the anchoring of a variety of virulence factors that contain specific sorting sequences to the surface of the bacterial cell wall envelope and participate in pathogenicity. The purpose of this study is to clarify the molecular mechanism of epigallocatechin-3-gallate (EGCG) inhibiting Streptococcus suis SrtA and provide more evidence for the development of novel anti- Streptococcus suis infections drugs. Through the SrtA substrate cleavage experiment, we found that the main component of green tea, EGCG, can effectively inhibit the enzyme activity of Streptococcus suis SrtA. Further, molecular docking and molecular dynamics simulation were used to clarify the molecular mechanism of its inhibitory effect, demonstrating that EGCG mainly interacts with amino acids at 113 and 115 to exert its inhibitory function. It was previously found that EGCG can inhibit the growth of S. suis and reduce the activity of suilysin and inhibit its expression. Our research reveals a new function of EGCG in S. suis infection. Our research proves that EGCG can effectively inhibit the transpeptidase activity of SrtA. We also clarify the accompanying molecular mechanism, providing more sufficient evidence for the use of EGCG as a potential lead compound against S. suis infection.