biostudies-literatureNakatsu GCancer Research UKHHS | NIH | National Cancer InstituteNCI NIH HHSHHS | NIH | National Cancer Institute (NCI)e0373224https://www.ebi.ac.uk/biostudies/studies/S-EPMC11796403biostudies-literatureUnknown16(2)<i>Fusobacterium</i> is a bacterium associated with colorectal cancer (CRC) tumorigenesis, progression, and metastasis. Fap2 is a fusobacteria-specific outer membrane galactose-binding lectin that mediates <i>Fusobacterium</i> adherence to and invasion of CRC tumors. Advances in omics analyses provide an opportunity to profile and identify microbial genomic features that correlate with the cancer-associated bacterial virulence factor Fap2. Here, we analyze genomes of <i>Fusobacterium</i> colon tumor isolates and find that a family of post-translational modification enzymes containing Fic domains is associated with Fap2 positivity in these strains. We demonstrate that Fic family genes expand with the presence of Fap2 in the fusobacterial pangenome. Through comparative genomic analysis, we fmBioVirulence factor discovery identifies associations between the Fic gene family and Fap2&lt;sup&gt;+&lt;/sup&gt; fusobacteria in colorectal cancer microbiomes.PMC11796403R01 CA154426R01CA154426Nakatsu GMichaud MHuttenhower CKo DGarrett WSMorgan XCFranzosa EAfalseVirulence factor discovery identifies associations between the Fic gene family and Fap2&lt;sup&gt;+&lt;/sup&gt; fusobacteria in colorectal cancer microbiomes.<i>Fusobacterium</i> is a bacterium associated with colorectal cancer (CRC) tumorigenesis, progression, and metastasis. Fap2 is a fusobacteria-specific outer membrane galactose-binding lectin that mediates <i>Fusobacterium</i> adherence to and invasion of CRC tumors. Advances in omics analyses provide an opportunity to profile and identify microbial genomic features that correlate with the cancer-associated bacterial virulence factor Fap2. Here, we analyze genomes of <i>Fusobacterium</i> colon tumor isolates and find that a family of post-translational modification enzymes containing Fic domains is associated with Fap2 positivity in these strains. We demonstrate that Fic family genes expand with the presence of Fap2 in the fusobacterial pangenome. Through comparative genomic analysis, we f2025-01-01T00:00:00Z2025 Feb2026-04-13T03:20:12.77Z2025-04-04T02:09:40.33ZS-EPMC117964033980786410.1128/mbio.03732-24