Characterization of the OMP biogenesis machinery in Fusobacterium nucleatum

Cottom, Claire Overly and Heinz, Eva and Erramilli, Satchal and Kossiakoff, Anthony and Slade, Daniel J. and Noinaj, Nicholas (2025) Characterization of the OMP biogenesis machinery in Fusobacterium nucleatum. Structure, 33 (11). 1878-1892.e5. ISSN 0969-2126 (https://doi.org/10.1016/j.str.2025.08.008)

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Abstract

F. nucleatum is a Gram-negative bacteria that causes oral infections and is linked to colorectal cancer. Pathogenicity relies on a type of β-barrel outer membrane protein (OMP) called an autotransporter. The biogenesis of OMPs is typically mediated by the barrel assembly machinery (BAM) complex. In this study, we investigate the evolution, composition, and structure of the OMP biogenesis machinery in F. nucleatum. Our bioinformatics and proteomics analyses indicate that OMP biogenesis in F. nucleatum is mediated solely by the core component BamA. The structure of FnBamA highlights distinct features, including four POTRA domains and a C-terminal 16-stranded β-barrel domain observed as an inverted dimer. FnBamA represents the original composition of the assembly machinery, and a duplication event that resulted in BamA and TamA occurred after the split of other lineages, including the Proteobacteria, from the Fusobacteria. FnBamA, therefore, likely serves a singular role in the biogenesis of all OMPs.

ORCID iDs

Cottom, Claire Overly, Heinz, Eva ORCID logoORCID: https://orcid.org/0000-0003-4413-3756, Erramilli, Satchal, Kossiakoff, Anthony, Slade, Daniel J. and Noinaj, Nicholas;