The Role of Streptococcus Gallolyticus Subspecies Gallolyticus In Colon Cancer Development

<p>Colorectal cancer (CRC) is the third most common cancer in men and women and is also the third most common cause of cancer death. A large body of evidence points towards the possibility that bacteria can have a significant impact on the development of cancer. It has been suggested that <em>Streptococcus gallolyticus </em>subsp<em>. gallolyticus</em>, a group D streptococci, may play a role in the development of CRC. <em>Sg</em>, formerly S. <em>bovis </em>biotype I, has been shown to be highly associated with CRC. In observing patients with either <em>Sg </em>bacteremia or endocarditis it was found that 25-80% of patients with <em>Sg </em>bacteremia had tumors and 18-62% of patients with <em>Sg </em>endocarditis had colonic neoplasias. However, other closely related Streptococcal strains, such as <em>S. pasterianus </em>and <em>S. infantarius</em>, have not been shown to have this strong association with CRC. In fact, it has been shown that biotype I is more often associated with CRC (94%) as compared to biotype II (18%). This knowledge has important clinical implications, and yet little is known about the role of <em>Sg </em>on CRC and the underlying mechanisms. Here we show that mice treated with <em>Sg </em>had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin level in colonic crypts compared to mice treated with control bacteria. <em>Sg </em>strains that promoted proliferation were also more efficient at adhering to CRC cell lines and colonizing a mouse model. Additionally, in human patients <em>Sg </em>was highly prevalent in CRC patients and tumor tissues had an increased <em>Sg </em>burden in comparison to normal adjacent tissues. These results provide exciting new information and establish a tumor-promoting role of <em>Sg </em>that involves specific bacterial and host factors.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2016

Author dc:creator

• Herold, Jennifer L

Contributors dc:contributor

• Yi Xu
• Magnus Hook
• Scott Kopetz

• Colorectal cancer
• microbiome
• Streptococcus gallolyticus
• Streptococcus bovis
• β-catenin
• tumorigenesis
• Bacteriology
• Cancer Biology
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/718

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1762