The assembly of a hybrid type IV secretion system by a Crohn’s disease-associated Escherichia coli strain

ABSTRACT: Type IV secretion systems (T4SSs) are central to bacterial pathogenesis due to their versatile functions. While traditionally known for their role in DNA transfer via conjugation and secretion of effector proteins, T4SSs have been shown to mediate biofilm formation in various bacteria. These biofilms are critical for the fitness of adherent-invasive strains of Escherichia coli (AIEC), which are commonly isolated from Crohn’s disease patients and are known for propelling gut inflammation. Many AIEC strains carry F-like plasmids encoding the IncF subgroup of T4SSs. Unlike minimized systems that comprise 12 core components, the IncF family has evolved into an expanded T4SS through the acquisition of additional genes that enhance conjugation. Here, we show that a biofilm-forming AIEC strain harbors an unusual IncF plasmid that lacks two conserved components otherwise considered essential for T4SS functionality. We demonstrate that this strain forms a natural hybrid T4SS, where the two components missing in the plasmid are supplied by a co-residing chromosomal T4SS present on an integrative and conjugative element (ICE). Using biochemical assays, we show that this functional machine is a mosaic of IncF and ICE-encoded proteins that co-operatively drive pilin polymerization and biofilm formation on epithelial cells. Furthermore, we show that a subpopulation of bacteria expresses the IncF and ICE-encoded genes in response to host cells, leading to the assembly of biofilms that promote AIEC fitness in the gut. Together, these findings uncover a crosstalk between two co-residing and evolutionary distant mobile genetic elements to form a hybrid T4SS that mediates biofilm biogenesis by a Crohn’s disease-associated pathogen.

INSTRUMENT(S):

ORGANISM(S): Escherichia Coli

SUBMITTER: Jonas Wong  

LAB HEAD: Wael Elhenawy

PROVIDER: PXD066462 | Pride | 2025-07-23

REPOSITORIES: Pride