The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammator...The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammatory bowel disease or colon cancer, commensal bacteria gain the ability to alter both the behavior of epithelial cells as well as their surrounding extra cellular matrix (ECM). While much work has been done to understand the effects of bacteria on diseased epithelial cells in the colon, very little has been done to understand their impact on the ECM. In our previous work, we have shown that topographical changes in the ECM on the luminal side of the colon have a profound influence on the behavior of colonic epithelial cells. However, we do not understand all of the mechanisms that lead to changes in the ECM topography. This study aimed to understand the role that commensal E. coli strains play in altering the ECM topography of type-1 collagen scaffolds. To do this, 1.2 mg/ml type 1 collagen scaffolds were infected with various commensal bacterial strains. At 24 hours post-infection collagen fiber dimensions and substrate topography were determined using standard molecular biology techniques and advanced imaging. Intriguingly, all of the commensal E. coli strains showed some form of substrate degradation. Especially in the case of commensal E. coli strain HS4, maximum nano-scaled protrusions were observed. This data suggests, for the first time, that studying the effects of bacteria alone on the ECM may be critical to improving our understanding of how the cellular microenvironment changes in both health and disease.展开更多
文摘The relationship between commensal bacteria and the epithelial cells lining the colon is normally symbiotic. However, in the setting of diseases which lead to a loss of the protective mucosal layer such as inflammatory bowel disease or colon cancer, commensal bacteria gain the ability to alter both the behavior of epithelial cells as well as their surrounding extra cellular matrix (ECM). While much work has been done to understand the effects of bacteria on diseased epithelial cells in the colon, very little has been done to understand their impact on the ECM. In our previous work, we have shown that topographical changes in the ECM on the luminal side of the colon have a profound influence on the behavior of colonic epithelial cells. However, we do not understand all of the mechanisms that lead to changes in the ECM topography. This study aimed to understand the role that commensal E. coli strains play in altering the ECM topography of type-1 collagen scaffolds. To do this, 1.2 mg/ml type 1 collagen scaffolds were infected with various commensal bacterial strains. At 24 hours post-infection collagen fiber dimensions and substrate topography were determined using standard molecular biology techniques and advanced imaging. Intriguingly, all of the commensal E. coli strains showed some form of substrate degradation. Especially in the case of commensal E. coli strain HS4, maximum nano-scaled protrusions were observed. This data suggests, for the first time, that studying the effects of bacteria alone on the ECM may be critical to improving our understanding of how the cellular microenvironment changes in both health and disease.