The human digestive tract is home to a host of natural bacteria that promote intestinal health. One of the functions of this so-called “good bacteria” is to provide protection from pathogens by competing with these invaders for access to the available nutrients that allow them to colonize.
Individuals who have colorectal cancer demonstrate a marked increase in colonization by opportunistic “bad“ bacteria. In fact, the link between colorectal cancer and a particular pathogen, Streptococcus gallolyticus, is so strong that many patients receive the cancer diagnosis following a colonoscopy ordered for the purpose of investigating an infection by S. gallolyticus.
Scientists believe that understanding the specific mechanisms that allow S. gallolyticus to abundantly colonize cancer-affected colorectal tissue may provide insight into testing protocols and allow for early detection. Researchers cultured S. gallolyticus on a medium that replicates the environment found in colon tumors.
They found that, compared to other species of intestinal bacteria, S. gallolyticus enjoyed a significant increase in growth rate and metabolic function when grown on this medium. Utilizing the most recent proteomic technology, researchers identified 176 protein spots with clinically significant fold changes and began peptide sequencing, resulting in the isolation of 78 unique proteins. Researchers then examined the metabolic pathways.
Most of these proteins were found to function in the metabolism of carbohydrates, amino acids, and nucleotides. Researchers applied global metabolic pathway mapping and spectroscopy to determine that S. gallolyticus colonies grown in spent tumor medium enjoyed a specific growth advantage because they preferentially consume glucose and glucose derivatives produced in tumor cells. Indeed, glucose metabolites and specific amino acids found in tumor cells (notably F6P, 3PG, and alanine) actually lend these colonies a competitive edge in terms of increased growth rate.
These findings begin to shed light on the observable increase in colonization by the opportunistic pathogen S. gallolyticus in patients with colorectal cancer as compared to individuals with healthy colons. This competitive growth advantage may prove to be an important factor in the creation of evaluative protocols for the early detection of colon cancer. With close to 150,000 new cases of colorectal cancer in the United States every year, this possibility represents an early win for the application of proteomic research.
Boleij, A., Dutilh, B. E., Kortman, G., Roelofs, R., Laarakkers, C. M., Engelke, U. F., & Tjalsma, H. (2012). Bacterial Responses to a Simulated Colon Tumor Microenvironment. Molecular & Cellular Proteomics. doi: 10.1074/mcp.M112.019315