Epigallocatechin Gallate Remodelling of Hfq Amyloid-Like Region Affects Escherichia coli Survival.

David Partouche,Omar El Hamoui,Véronique Arluison,Frank Wien,Sylvain Trépout,Marianne Bombled,Florian Turbant,Camille Campidelli

doi:10.3390/pathogens7040095

Abstract

Hfq is a pleiotropic regulator that has key roles in the control of genetic expression. The protein noticeably regulates translation efficiency and RNA decay in Gram-negative bacteria, due to the Hfq-mediated interaction between small regulatory noncoding RNA and mRNA. This property is of primary importance for bacterial adaptation and virulence. We have previously shown that the Hfq E. coli protein, and more precisely its C-terminal region (CTR), self-assembles into an amyloid-like structure. In the present work, we demonstrate that epigallocatechin gallate (EGCG), a major green tea polyphenol compound, targets the Hfq amyloid region and can be used as a potential antibacterial agent. We analysed the effect of this compound on Hfq amyloid fibril stability and show that EGCG both disrupts Hfq-CTR fibrils and inhibits their formation. We show that, even if EGCG affects other bacterial amyloids, it also specifically targets Hfq-CTR in vivo. Our results provide an alternative approach for the utilisation of EGCG that may be used synergistically with conventional antibiotics to block bacterial adaptation and treat infections.

Highlights

Antibiotic resistance occurs when a compound has lost its ability to kill bacteria
To investigate the possibility that Hfq functional amyloids can be remodeled in vitro, we screened the effect of epigallocatechin gallate (EGCG) on Hfq-C-terminal region (CTR) fibrils using transmission electron microscopy (TEM, see Section 4.3)
As a model we first used the 11 amino acid residues peptide corresponding to the Hfq amyloid region only, referred to as Hfq CTR11 [42]

Summary

Introduction

Antibiotic resistance occurs when a compound has lost its ability to kill bacteria. This problem is critical for public health and many efforts have been done to modify and improve existing antibiotics. Antibacterial agents use four main mechanisms; inhibition of cell wall synthesis (β-lactams), inhibition of protein synthesis (aminoglycosides, tetracyclines), inhibition of nucleic acid synthesis (quinolones) or inhibition of metabolic pathways (sulfonamides). The main problem with this therapeutic approach is the development of new acquired resistances. These usually involve mutations in genes of the antibiotic target or acquisition of foreign DNA, allowing antibiotic modification, destruction or efflux [1]. The search for novel antibacterial-targets is of utmost importance

Methods

Results

Discussion

Conclusion