Relevance. Yersinia pseudotuberculosis is a causative agent of pseudotuberculosis, a disease with polymorphism of clinical manifestation that is determined by the presence of specific virulence determinants: plasmid pVM82, pathogenicity islands HPI and YAPI, and superantigen YPM. Occurrence of new determinants depends on horizontal transfer of mobile genetic elements, hence, systems regulating horizontal transfer participate in evolution of pathogenic species. CRISPR-Cas is and adaptive protection system of prokaryotes against mobile genetic elements. Aim. The study analyzed an interaction between CRISPR-loci of Y. pseudotuberculosis and virulence determinants. Results. 86% of strains includes three CRISPR-loci: YP1, YP2, and YP3. Length of locus YP3 mostly depends on presence of virulence determinants in strains of Y. pseudotuberculosis serotype O:1b. Strains with virulence genes are able to cause a severe form of pseudotuberculosis and have longer locus than strains without determinants. Conclusion. Therefore, CRIPSRCas system of Y. pseudotuberculosis may participate in formation of a certain strain genotype that defines clinical manifestation of pseudotuberculosis.
Nowadays multiple heterogeneous chemicals affect the human body. They include drugs, household chemicals, dyes, food supplements and others. The human organism can modify, inactivate, and eliminate the chemicals by biotransformation enzymes. But it is well known that biotransformation can lead to toxification phenomenon. Individuals differ from each other by the rate of chemical modification that promotes accumulation of toxins and carcinogens in some patients. An N-acetyltransferase 2 enzyme participates in the aromatic amines second phase metabolism. This work reviews the acetyltransferase gene polymorphism possible role in diseases development including drug-induced organs damage.Gene of acetyltransferase has polymorphisms associated with two haplotypes of fast and slow substrate acetylation. Gene alleles combine in three genotypes: fast, intermediate, and slow acetylators. Acetylation rate plays a significant role in side effects development during tuberculosis treatment and cancer pathogenesis. Recently, new data described the role of enzyme in development of non-infectious diseases in the human. Scientists consider that slow acetylation genotype in combination with high xenobiotic load result in accumulation of toxic substances able to damage cells.Therefore, acetyltransferase genotyping helps to reveal risk groups of cancer and non-infectious disease development and to prescribe more effective and safe doses of drugs.
The results of this study include Yersinia pseudotuberculosis CRISPR/Cas system structure analysis. CRISPR/Cas system is a specific adaptive protection against heterogeneous genetic elements. The object of research was the complete genome of Y. pseudotuberculosis IP32953 (NC_006155). CRISPR/Cas system screening was performed by program modelling methods MacSyFinder ver. 1.0.2. CRISPR loci screening and analyzing were carried out by program package: CRISPR Recognition tool (CRT), CRISPI: a CRISPR Interactive database, CRISPRFinder, and PilerCR. Spacer sequences were used in order to find protospacers in ACLAME, GenBank-Phage and RefSeq-Plasmid databases by BLASTn search algorithm. Protospacer sequences could be found in genomes of phages, plasmids and bacteria. In last case complete genomes of bacteria were analyzed by online-tool PHAST: PHAge Search Tool. Y. pseudotuberculosis IP329353 has CRISPR/Cas system that consists of one sequence of cas-genes and three loci. These loci are far away from each other. Locus YP1 is situated in close proximity to cas-genes. Protospacers were found in genomes of Y. pseudotuberculosis PB1/+, Y. intermedia Y228, Y. similis str. 228, Salmonella phage, Enterobacteria phage, Y. pseudotuberculosis IP32953 plasmid pYV and plasmid of Y. pseudotuberculosis IP31758. Thus, the combination of four program methods allows finding CRISPR/Cas system more precisely. Spacer sequences could be used for protospacer screening.
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