While
high-colibactin-producing Escherichia coli is thought
to be associated with colorectal oncogenesis, this study
is complicated part due to an inability to isolate colibactin adequately.
Here, we created fluorescent probes activated by ClbP, the colibactin-maturing
peptidase, to identify high-colibactin-producing strains. Our probe
served as a valuable clinical diagnostic tool that allowed simple
high-throughput diagnostic screening of clinical samples. Furthermore,
the probe also allowed identification of high-colibactin producers
that would help advance our understanding of colibactin biosynthesis.
Rings or arcs of fungus-regulated plant growth occurring on the floor of woodlands and grasslands are commonly called “fairy rings”. Fairy chemicals, 2-azahypoxanthine (AHX), imidazole-4-carboxamide (ICA), and 2-aza-8-oxohypoxanthine (AOH), are plant growth regulators involved in the phenomenon. The endogeny and biosynthetic pathways of AHX and AOH in plants have already been proven, however, those of ICA have remained unclear. We developed a high-sensitivity detection method for FCs including ICA and the endogenous ICA was detected in some plants for the first time. The quantitative analysis of the endogenous level of ICA in rice and Arabidopsis were performed using
13
C-double labeled ICA. In addition, the incorporation experiment and enzyme assay using the labeled compound into rice and partially purified fraction of rice indicated that ICA is biosynthesized from 5-aminoimidazole-4-carboxamide (AICA), a metabolite on the purine metabolic pathway. The relationship between ICA and AHX was also discussed based on quantitative analysis and gene expression analysis.
We investigated the relationship between colibactin-producing (clb +) Escherichia coli and colorectal adenocarcinoma. In total, 729 E. coli colonies were isolated from tumor and surrounding non-tumor regions in resected specimens from 34 Japanese patients; 450 colonies were from tumor regions and 279 from non-tumor regions. clb + bacteria were found in tumor regions of 11 patients (11/34, 32.4%) and in non-tumor regions of seven of the 11 (7/34, 20.6%). The prevalence of clb + isolates was 72.7% (327/450) and 44.1% (123/279) in tumor and non-tumor regions, respectively. All the recovered clb + isolates belonged to the phylogenetic group B2 and were the most predominant type in tumor regions. Hemolytic (αhemolysin-positive, hlyA +) and non-hemolytic (α-hemolysin-negative, hlyA-) clb + isolates were obtained from patient #19; however, the prevalence of hlyA + clb + isolates was significantly higher in tumor regions (35/43, 81.4%) than in non-tumor regions (3/19, 15.8%). Moreover, a significantly higher production of N-myristoyl-D-asparagine, a byproduct of colibactin biosynthesis, was observed in hlyA + clb + isolates than in hlyAclb + isolates. Our results suggest that hlyA + clb + E. coli may have a selective advantage in colorectal colonization, consequently playing a role in carcinogenesis. The presence of hlyA + clb + bacteria in healthy individuals is a risk marker of colorectal cancer.
The metabolism of imidazole-4-carboxamide (ICA) in plants has been unknown. Two metabolites (1 and 2) were isolated from ICA-treated rice, and their structures were determined by spectroscopic analysis including the single-crystal X-ray diffraction technique and synthesis. The ribotide of ICA (3), whose existence was predicted, was also synthesized and detected from the treated rice by LC−MS/ MS. These results indicated that rice might interconvert ICA, 1, and 3 to regulate the biological activity.
During the course of our investigations of fairy chemicals (FCs), we found S-ICAr-H (8a), as a metabolite of imidazole-4-carboxamide (ICA) in rice and yeast (Saccharomyces cerevisiae). In order to determine its absolute configuration, an efficient synthetic method of 8a was developed. This synthetic strategy was applicable to the preparation of analogues of 8a that might be biologically very important, such as S-ICAr-M (9), S-AICAr-H (10), and S-AICAr-M (11).
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