IADR Abstract Archives

Specific Colonization of Oral Fusobacterium nucleatum in Colorectal Carcinoma

Objectives: Fusobacterium nucleatum (Fn) is a gram-negative, anaerobic, preriodontopathogen that is involved in preterm births and colorectal carcinoma (CRC). This study aims to investigate the mechanisms that mediate CRC colonization by Fn.
Methods: Human CRC and adjacent normal tissue samples, human cell lines, and murine orthotopic CT26-Luc colorectal cancer model were used to investigate fusobacterial attachment to, and colonization of CRC.
Results: Fusobacterial localization in the colon is tumor-dependent, as injected fusobacteria were undetected in the colons of tumor-free mice. CRC colonization is species specific as the gram-negative, periodontitis-related pathogen Prophyromonas gingivalis fails to colonize CRC.
Gal-GalNAc was found to be highly expressed in human and mouse CRC compared to adjacent normal tissues. Binding of FITC-labeled Fn corresponded with the levels of Gal-GalNAc and co-localized with Gal-GalNAc in the tumor. Fap2 was found to be a fusobacterial Gal-GalNAc lectin. Fap2 deficient Fn mutants were impaired in binding to murine and human CRC cell lines. Tumor colonization by Fap2-deficient Fn mutants was significantly lower than that of the Fap2-sufficient parental strain.
Conclusions: Our results demonstrate that the fusobacterial Fap2 lectin binds to Gal-GalNAc overexpressed on CRC and mediates the tumor-specific attachment of Fn. Understanding the interaction of Fn with CRC, may enable future development of novel diagnostic and therapeutic agents for this disease.
IADR/PER Congress
2016 IADR/PER Congress (Jerusalem, Israel)
Jerusalem, Israel
2016
0047
Microbiology/Immunology
  • Abed, Jawad  ( Hebrew university of Jerusalem , Nazareth , Israel )
  • Emgård, Johanna  ( Hebrew university of Jerusalem , Nazareth , Israel )
  • Chaushu, Stella  ( Hebrew university of Jerusalem , Nazareth , Israel )
  • Garrett, Wendy  ( Harvard T.H. Chan School of Public Health , Boston , Massachusetts , United States )
  • Bachrach, Gilad  ( The Hebrew University-Hadassah School of Dental Medicine , Jerusalem , Non-US/Canada , Israel )
  • NONE
    Oral Session
    Microbiology/Immunology II
    Wednesday, 09/21/2016 , 09:00AM - 10:30AM