# Enterohaemorrhagic Escherichia coli AdhE spirosome length correlates with enzymatic directionality and is perturbed by salicylidene acylhydrazides

## TL;DR

This study explores how a compound called ME0054 affects the structure and function of the AdhE enzyme in harmful E. coli, potentially leading to new treatments.

## Contribution

The study reveals that ME0054 perturbs AdhE spirosomes and alters enzymatic directionality, offering new insights into anti-virulence therapy.

## Key findings

- AdhE spirosomes form helicoidal filaments that regulate enzymatic reaction direction.
- ME0054 binds to and perturbs AdhE spirosomes, enhancing ethanol to acetyl-CoA conversion.
- Understanding ME0054's mechanism could aid in developing anti-virulence inhibitors.

## Abstract

Enterohaemorrhagic Escherichia coli causes sporadic, and sometimes large-scale, food poisoning outbreaks, for which antibiotic treatment in humans is contraindicated. As an alternative form of therapy, previous studies developed the family of salicylidene acylhydrazide (SA) anti-virulence compounds. One target of the SA compounds is AdhE, an enzyme that converts acetyl-CoA to ethanol and vice versa. AdhE oligomerizes, forming helicoidal filaments, heterogeneous in length, called spirosomes. We show it is possible to only partially fractionate AdhE spirosomes because in vitro they oligomerize in the absence of stimuli, and that spirosome formation is necessary to regulate the direction of AdhE enzymatic reactions. We also show that the SA compound ME0054 binds and perturbs AdhE spirosomes, enhancing the conversion of ethanol to acetyl-CoA. This mechanistic understanding of how ME0054 impacts AdhE function will help in the development of SA compounds as novel anti-virulence inhibitors.