Molecular screening and genetic diversity analysis of anticancer Azurin-encoding and Azurin-like genes in human gut microbiome deduced through cultivation-dependent and cultivation-independent studies
| Autor: | Thanh Tra Nguyen, Michael Sylvester Packianather, Chi Hieu Le, Van Duy Nguyen, Thu Thuy Pham |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Microbiology (medical) Adolescent Computational biology Biology Microbiology Feces Young Adult 03 medical and health sciences Azurin Genotype Protein biosynthesis Humans Microbiome Child Gene Phylogeny 030304 developmental biology 0303 health sciences Genetic diversity 030306 microbiology Human microbiome Genetic Variation Culture Media Gastrointestinal Microbiome Metagenomics Pseudomonas aeruginosa Female |
| Zdroj: | International Microbiology. 22:437-449 |
| ISSN: | 1618-1905 1139-6709 |
| DOI: | 10.1007/s10123-019-00070-8 |
| Popis: | Azurin, a bacteriocin produced by a human gut bacterium Pseudomonas aeruginosa, can reveal selectively cytotoxic and induce apoptosis in cancer cells. After overcoming two phase I trials, a functional region of Azurin called p28 has been approved as a drug for the treatment of brain tumor glioma by FDA. The present study aims to improve a screening procedure and assess genetic diversity of Azurin genes in P. aeruginosa and Azurin-like genes in the gut microbiome of a specific population in Vietnam and global populations. Firstly, both cultivation-dependent and cultivation-independent techniques based on genomic and metagenomic DNAs extracted from fecal samples of the healthy specific population were performed and optimized to detect Azurin genes. Secondly, the Azurin gene sequences were analyzed and compared with global populations by using bioinformatics tools. Finally, the screening procedure improved from the first step was applied for screening Azurin-like genes, followed by the protein synthesis and NCI in vitro screening for anticancer activity. As a result, this study has successfully optimized the annealing temperatures to amplify DNAs for screening Azurin genes and applying to Azurin-like genes from human gut microbiota. The novelty of this study is the first of its kind to classify Azurin genes into five different genotypes at a global scale and confirm the potential anticancer activity of three Azurin-like synthetic proteins (Cnazu1, Dlazu11, and Ruazu12). The results contribute to the procedure development applied for screening anticancer proteins from human microbiome and a comprehensive understanding of their therapeutic response at a genetic level. |
| Databáze: | OpenAIRE |
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