Luteolin Inhibits Invasion of Listeria monocytogenes by Interacting with SortaseA and InternalinB

TL;DR

Luteolin prevents Listeria monocytogenes from invading host cells by interacting with key bacterial proteins, offering a potential treatment for foodborne infections.

Contribution

Luteolin is shown to inhibit Listeria monocytogenes invasion by interacting with SortaseA and InternalinB, offering a novel antimicrobial strategy.

Findings

Luteolin inhibits purified LM SortaseA activity and interacts with its active sites.

Luteolin binds to InternalinB's receptor interface, potentially blocking host cell invasion.

Luteolin reduces LM infection symptoms in Galleria mellonella without affecting bacterial growth.

Abstract

Listeria monocytogenes (LM) is a lethal foodborne intracellular pathogen. Internalins A and B (inlA and inlB) are critical virulence factors that promote LM’s adhesion and invasion into host cells. InlA is covalently anchored to the cell wall by LM SortaseA (SrtA), while inlB is anchored to the cell wall via non-covalent bonds. Therefore, inhibiting SrtA and inlB is expected to suppress LM’s adhesion and invasion of host cells, enabling the prevention and control of infections. This study demonstrated that Luteolin inhibited the activity of purified LM SrtA protein in vitro. Interactive mechanism analysis indicated that Luteolin generates interaction with the critical active sites of SrtA, which may affect its binding to its natural substrates, thereby reducing the anchoring of inlA on the cell wall and achieving the inhibition of bacterial adhesion and invasion. In addition, Luteolin binds to the groove at the binding interface between inlB and its host receptor. The key residues in inlB that interact with the host receptor form weak interactions (Hydrogen bonds and van der Waals interactions) with Luteolin, this binding may inhibit their binding, suppressing LM’s adhesion and invasion of host cells. At the tested concentrations, Luteolin did not affect the growth of LM, but remarkably reduced the mortality and alleviated the infection symptoms of LM-infected Galleria mellonella. These results provide additional theoretical evidence for the application of Luteolin in the prevention and control of LM infections, which is expected to accelerate its application progress.

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