Potential quorum-sensing inhibitor of Hafnia alvei H4-theaflavin-3,3´-digallate analyzed by virtual screening and molecular simulation

Hafnia species can cause food spoilage via the quorum-sensing (QS) system. Thus, strategies that target QS in these bacteria might be a good approach to safeguard the quality of processed food. In this study, the amino acid sequence of the LasI _Ha protein, a key QS regulator from Hafnia alvei H4, was used to construct its 3D structure for the virtual screening of potential QS inhibitors (QSIs) from the Bioactive Compound database. Four potential QSIs were obtained, and these were all theaflavins (TFs). Among them, theaflavin-3,3´-digallate (TF3) was found to outperform the Others, displaying a higher docking score according to molecular docking analysis, and required only a sub-minimal inhibitory concentration (31.25 mM) to cause a significant decrease in the production of the autoinducer N-acyl homoserine lactone in H. alvei H4 and up to 60.5% inhibition of its motility. Furthermore, molecular simulation results indicated that TF3 could stably bind to a cavity within LasI _Ha to form stable hydrogen bonds and hydrophobic interactions with various key residues of the protein to exert the inhibitory effect. Thus, TF3 may be considered a potential compound to protect against food spoilage caused by H. alvei H4 via the quorum quenching. IMPORTANCE Hafnia alvei, the main strain studied in this paper, is often isolated from spoiled foods, especially refrigerated protein-based raw foods, and is generally considered to be a spoilage bacterium whose spoilage-causing properties may be closely related to its own very strong population-sensing activity, so the strategy of quorum quenching against H. alvei H4 may be a good way to guarantee the quality of processed foods. Given the current global requirements for food safety and quality, coupled with negative consumer perceptions of the excessive inclusion of synthetic chemicals in food products, the use of natural compounds as QSIs in the storage of aquatic food products would seem more attractive.

Hafnia alvei; TF3; molecular docking; molecular dynamics simulation; quorum sensing inhibitor; virtual screening.