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posted on 2023-03-30, 23:48 authored by Ye Jin, Senwei Tang, Weilin Li, Siew Chien Ng, Michael W.Y. Chan, Joseph J.Y. Sung, Jun Yu Verification of computational E. coli typing based on fimH mutation patterns. (A) Estimation of the factorization rank r in nonnegative matrix factorization (NMF). NMF analysis using 4 as the factorization rank r revealed that fimH could be classified into four types. (B) Consensus sequence of each type of fimH. Consensus sequences were illustrated by WebLogo using stacks of symbols. The size of symbols indicates the relative frequency of each base at that position.
Funding
863 Program China
973 Program China
National Natural Science Foundation of China (NSFC) for Young Scientists
Shenzhen Technology and Innovation Project Fund
Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute
History
ARTICLE ABSTRACT
Bacterial infection is linked to colorectal carcinogenesis, but the species that contribute to a protumorigenic ecology are ill-defined. Here we report evidence that α-hemolysin–positive (hly+) type I Escherichia coli (E. coli) drives adenomagenesis and colorectal cancer in human females but not males. We classified E. coli into four types using a novel typing method to monitor fimH mutation patterns of fecal isolates from adenoma patients (n= 59), colorectal cancer patients (n= 83), and healthy subjects (n= 85). hly+ type I E. coli was found to be relatively more prevalent in stools from females with adenoma and colorectal cancer, correlating with poor survival in colorectal cancer patients. In mechanistic studies in female mice, we found that hly+ type 1 E. coli activated expression of the glucose transporter GLUT1 and repressed expression of the tumor suppressor BIM. hly-encoded alpha hemolysin partially accounted for these effects by elevating the levels of HIF1α. Notably, colon tumorigenesis in mice could be promoted by feeding hly+ type I E. coli to female but not male subjects. Collectively, our findings point to hemolytic type I E. coli as a candidate causative factor of colorectal cancer in human females, with additional potential as a biomarker of disease susceptibility. Cancer Res; 76(10); 2891–900. ©2016 AACR.
