Anti-virulence activity and immunomodulation of Oreoch-1 against enteroinvasive Escherichia coli infection.

Enteroinvasive Escherichia coli (EIEC) is a major causative agent of infectious diarrhea, associated with morbidity and mortality. The induction of host damage relies on specific virulence factors harbored by the large virulence plasmid pINV. Considering the recent outbreaks and the alarming emergence of drug-resistant EIEC strains, innovative interventional approaches are required. Anti-virulence interference appears promising as it targets bacterial virulence rather than viability, thereby posing a lower risk of inducing drug resistance. In this context, antimicrobial peptides (AMPs), usually short, cationic molecules, have emerged for their wide spectrum of activity. This study demonstrates the anti-virulence and immunomodulatory potential of Oreoch-1, a 23-mer cationic peptide derived from the Nile tilapia (Oreochromis niloticus), in an in vitro model of EIEC infection. We challenged EIEC ATCC 43983 strain with the peptide (3.125-25 μM) via broth microdilution method, assessing its slight activity in the range 6.25-12.5 μM. Then, we evaluated the ability of Oreoch-1 to interfere with the bacterial invasion process in the colon carcinoma cell line (Caco-2). We specifically assessed the ability of Oreoch-1 to modulate key virulence factors of EIEC, including ial, icsA, icsB, ipaB, ipaC, virB, and virF, as well as the expression of inflammatory cytokines such as IL-6, IL-8, IL-1β, TNF-α, and TGF-β. These factors play crucial roles in the infection process from both the bacterial and host perspectives. Given our promising results, Oreoch-1 may emerge as a potential novel antimicrobial peptide that addresses the concerning issue of widespread drug resistance.