# Bioprospecting of inhibitors of EPEC virulence from metabolites of marine actinobacteria from the Arctic Sea

## TL;DR

This study explores marine actinobacteria from the Arctic Sea for compounds that can inhibit the virulence of a harmful gut bacteria, EPEC, which causes serious infections in infants.

## Contribution

The study introduces a novel bioassay-guided approach to identify antivirulence compounds from Arctic marine actinobacteria.

## Key findings

- A compound from a Kocuria strain inhibits EPEC-induced actin polymerization without affecting bacterial growth.
- A growth-inhibiting compound was identified in a Rhodococcus strain.
- A large phospholipid and a likely antimicrobial peptide were isolated and characterized.

## Abstract

A considerable number of antibacterial agents are derived from bacterial metabolites. Similarly, numerous known compounds that impede bacterial virulence stem from bacterial metabolites. Enteropathogenic Escherichia coli (EPEC) is a notable human pathogen causing intestinal infections, particularly affecting infant mortality in developing regions. These infections are characterized by microvilli effacement and intestinal epithelial lesions linked with aberrant actin polymerization. This study aimed to identify potential antivirulence compounds for EPEC infections among bacterial metabolites harvested from marine actinobacteria (Kocuria sp. and Rhodococcus spp.) from the Arctic Sea by the application of virulence-based screening assays. Moreover, we demonstrate the suitability of these antivirulence assays to screen actinobacteria extract fractions for the bioassay-guided identification of metabolites. We discovered a compound in the fifth fraction of a Kocuria strain that interferes with EPEC-induced actin polymerization without affecting growth. Furthermore, a growth-inhibiting compound was identified in the fifth fraction of a Rhodococcus strain. Our findings include the bioassay-guided identification, HPLC-MS-based dereplication, and isolation of a large phospholipid and a likely antimicrobial peptide, demonstrating the usefulness of this approach in screening for compounds capable of inhibiting EPEC virulence.