Bacterial responses to a simulated colon tumor microenvironment.
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.
Department of Laboratory Medicine/830, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands.
Annemarie
A
Boleij
Bas E
BE
Dutilh
Guus A M
GA
Kortman
Rian
R
Roelofs
Coby M
CM
Laarakkers
Udo F
UF
Engelke
Harold
H
Tjalsma
D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D000409:Alanine / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology*; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D053858:Metabolic Networks and Pathways / Q000502:physiology; D055432:Metabolomics; D020543:Proteome; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D059016:Tumor Microenvironment
D001426:Bacterial Proteins; D017077:Culture Media, Conditioned; D020543:Proteome; D005947:Glucose; D000409:Alanine