Modeling the anti-adhesive role of punicalagin against listeria monocytogenes from the analysis of the interaction between internalin A and E-cadherin

Listeria monocytogenes poses health threats due to its resilience and potential to cause severe infections, especially in vulnerable populations. Plant extracts and/or phytocomplexes have demonstrated the capability of natural compounds in mitigating L. monocytogenes virulence. Here we explored the suitability of a computational pipeline envisioned to identify the molecular determinants for the recognition between the bacterial protein internalin A (InlA) and the human E-cadherin (Ecad), which is the first step leading to internalization. This pipeline consists of molecular docking and extended atomistic molecular dynamics simulations to identify key interaction clusters between InlA and Ecad. It exploits this information in the screening of chemical libraries of natural compounds that might competitively interact with InIA and hence impede the formation of the InIA–Ecad complex. This strategy was effective in providing a molecular model for the anti-adhesive activity of punicalagin and disclosed two natural phenolic compounds with a similar interaction pattern. Besides elucidating key aspects of the mutual recognition between InIA and Ecad, this study provides a molecular basis about the mechanistic underpinnings of the anti-adhesive action of punicalagin that enable application against L. monocytogenes.