A conserved protein, BcmA, mediates motility, biofilm formation, and host colonisation in Adherent Invasive Escherichia coli

Abstract

Adherent Invasive Escherichia coli (AIEC) is a non-diarrhoeagenic intestinal E. coli pathotype associated with Crohns Disease. AIEC pathogenesis is characterised by biofilm formation, adhesion to and invasion of intestinal epithelial cells, and intracellular replication within epithelial cells and macrophages. Here, we identify and characterise a protein in the prototypical AIEC strain LF82 which is required for efficient biofilm formation and dispersal - LF82_p314. LF82 {Delta}LF82_314 have defective swimming and swarming motility, indicating LF82_p314 is important for flagellar-mediated motility, and thus surface colonisation and biofilm dispersal. Flagellar morphology and chemotaxis in liquid appear unaffected by deletion of LF82_314, suggesting LF82_p314 does not elicit an effect on flagella biogenesis or environmental sensing. Flagellar motility has been implicated in AIEC virulence, therefore we assessed the role of LF82_p314 in host colonisation using a Caenorhabditis elegans model. We found that LF82 {Delta}LF82_314 have an impaired ability to colonise the C. elegans compared to wild-type LF82. Phylogenetic analysis showed that LF82_314 is conserved in several major enterobacterial pathogens, and suggests the gene may have been acquired horizontally in several genera. Our data suggests LF82_p314 may be a novel component in the flagellar motility pathway and is a novel determinant of AIEC colonisation. Our findings have potential implications not only for the pathogenesis of Crohns Disease, but also for the course of infection in several major bacterial pathogens. We propose a new designation for LF82_314, biofilm coupled to motility A, or bcmA.\n\nAuthor summaryAdherent Invasive Escherichia coli (AIEC) are a group of bacteria implicated in the pathogenesis of Crohns Disease, a chronic inflammatory bowel disease with no cure. Critical to the process of many bacterial infections is the ability of bacteria to swim towards and colonise the host surface using specialised, propeller-like appendages called flagella. In this paper, we describe a novel protein - LF82_p314 (BcmA) - which is required for efficient flagella-mediated motility and surface colonisation in AIEC. Using a nematode worm (Caenorhabditis elegans) infection model, we show that LF82_p314 enables effective colonisation of the C. elegans gut, suggesting a role for the protein during human infection. These findings indicate BcmA is significant for initial colonisation of the human gut by AIEC, and therefore the onset of Crohns Disease.