Structure‐Based Annotation by AlphaFold3 Predictions of the Francisella halioticida T6SS Encoded in the Francisella Pathogenicity Island

Abstract

ABSTRACT Francisella halioticida has emerged as a significant pathogen of cultured molluscs, causing substantial economic losses due to mass mortalities. The Francisella Pathogenicity Island encodes a Type VI secretion system essential for virulence and intracellular persistence. However, the F. halioticida pathogenicity island shows marked sequence divergence from well‐characterized Francisella strains, limiting the use of conventional sequence‐based annotation. This study performed a comprehensive structure‐based annotation of the F. halioticida pathogenicity island using AlphaFold3 predictions combined with systematic structural similarity searches. This approach identified five previously uncharacterized FPI components and their respective T6SS homologues. Notably, F. halioticida lacks the IglF protein and the N‐terminal α‐helix extension of IglG but retains a nearly complete and functionally coherent Type VI secretion system architecture.