Apomorphine Targets the Pleiotropic Bacterial Regulator Hfq.

Florian Turbant,Frank Wien,Véronique Arluison,Sylvain Trépout,Théa Legoubey,David Partouche,Omar El Hamoui

doi:10.3390/antibiotics10030257

Abstract

Hfq is a bacterial regulator with key roles in gene expression. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, thanks to its binding to small regulatory noncoding RNAs. This property is of primary importance for bacterial adaptation and survival in hosts. Small RNAs and Hfq are, for instance, involved in the response to antibiotics. Previous work has shown that the E. coli Hfq C-terminal region (Hfq-CTR) self-assembles into an amyloid structure. It was also demonstrated that the green tea compound EpiGallo Catechin Gallate (EGCG) binds to Hfq-CTR amyloid fibrils and remodels them into nonamyloid structures. Thus, compounds that target the amyloid region of Hfq may be used as antibacterial agents. Here, we show that another compound that inhibits amyloid formation, apomorphine, may also serve as a new antibacterial. Our results provide an alternative in order to repurpose apomorphine, commonly used in the treatment of Parkinson’s disease, as an antibiotic to block bacterial adaptation to treat infections.

Highlights

Antibiotic resistance happens when a bacterium fights a compound developed to kill it
To investigate the possibility that the Hfq C-terminal region (Hfq-C-terminal region (CTR)) amyloid can be affected by apom phine in vitro, we first screened its effect on Hfq-CTR preformed fibrils using transmiss electron microscopy (TEM)
Disruption of Hfq CTR Amyloid Fibrils by Apomorphine In Vitro amyloid interference was first tested on preformed Hfq-CTR fibrils

Summary

Introduction

Antibiotic resistance happens when a bacterium fights a compound developed to kill it. Bacteria that have a mutation allowing them to survive in the presence of an antibiotic will be selected from others This results in the constant emergence of new resistant pathogens that have acquired new resistance mechanisms. Some bacterial strains have acquired resistance to more or less all existing antibiotics, which use four main mechanisms (i.e., inhibition of cell wall, protein or nucleic acid synthesis, or of metabolic pathways such as folate synthesis). This acquisition of resistance may consist in antibiotic modification, destruction or efflux [2]. This strategy resulted in a rapid new resistance acquisition

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Conclusion