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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 E. coli typing based on fimH mutation patterns of fecal E. coli isolates. (A) Cluster analysis of single-nucleotide polymorphisms (SNP) of 711 fimH sequences. At the bottom of the figure are point mutations and their positions relative to the start codon of fimH. Red color represents that the mutations occur; blue color represents that the mutations do not occur. The horizontal box indicates the mutation pattern of type1-fimH. The vertical box indicates SNPs that are specific to type1-fimH and absent from the other types of fimH. (B) Distribution of the four types of E. coli in different subject groups. Each column represents a subject; each row represents fimH types of randomly selected fecal E. coli isolates. Color scheme: purple, type 1; blue, type 2, orange, type 3, green, type 4. (C) Percentage of subjects positive with each type of E. coli in different subject groups. H, the healthy subjects serving as controls; AD, patients with adenoma; CRC, patients with colorectal cancer. ***P < 0.001.
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.
