Bacterial responses to a simulated colon tumor microenvironment

Mol Cell Proteomics. 2012 Oct;11(10):851-62. doi: 10.1074/mcp.M112.019315. Epub 2012 Jun 19.


One of the few bacteria that have been consistently linked to colorectal cancer (CRC) is the opportunistic pathogen Streptococcus gallolyticus. Infections with this bacterium are generally regarded as an indicator for colonic malignancy, while the carriage rate of this bacterium in the healthy large intestine is relatively low. We speculated that the physiological changes accompanying the development of CRC might favor the colonization of this bacterium. To investigate whether colon tumor cells can support the survival of S. gallolyticus, this bacterium was grown in spent medium of malignant colonocytes to simulate the altered metabolic conditions in the CRC microenvironment. These in vitro simulations indicated that S. gallolyticus had a significant growth advantage in these spent media, which was not observed for other intestinal bacteria. Under these conditions, bacterial responses were profiled by proteome analysis and metabolic shifts were analyzed by (1)H-NMR-spectroscopy. In silico pathway analysis of the differentially expressed proteins and metabolite analysis indicated that this advantage resulted from the increased utilization of glucose, glucose derivates, and alanine. Together, these data suggest that tumor cell metabolites facilitate the survival of S. gallolyticus, favoring its local outgrowth and providing a possible explanation for the specific association of S. gallolyticus with colonic malignancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / microbiology
  • Adenocarcinoma / pathology
  • Alanine / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Line, Tumor
  • Colon / metabolism*
  • Colon / microbiology
  • Colon / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / microbiology
  • Colorectal Neoplasms / pathology
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology*
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression
  • Glucose / metabolism
  • Host-Pathogen Interactions
  • Humans
  • Magnetic Resonance Spectroscopy
  • Metabolic Networks and Pathways / physiology
  • Metabolomics
  • Proteome
  • Streptococcus / drug effects
  • Streptococcus / genetics
  • Streptococcus / growth & development
  • Streptococcus / metabolism*
  • Tumor Microenvironment


  • Bacterial Proteins
  • Culture Media, Conditioned
  • Proteome
  • Glucose
  • Alanine