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