A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages

Abstract

Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin–antitoxin systems. Another catalog of 1,573 M. tuberculosis isolates of different lineages has been developed. The developed SNP-calling program has identified 3,563 nonsynonymous SNPs. The constructed SNP-based phylogeny reflected the evolutionary relationship between lineages and detected new sublineages. SNP analysis of sublineage F15/LAM4/KZN revealed four lineage-specific mutations in cyp125, mce3B, vapC25, and vapB34. The Ural lineage has been divided into two geographical clusters based on different SNPs in virulence genes. A new sublineage, B0/N-90, was detected inside the Beijing-B0/W-148 by SNPs in irtB, mce3F and vapC46. We have found 27 members of B0/N-90 among the 227 available genomes of the Beijing-B0/W-148 sublineage. Whole-genome sequencing of strain B9741, isolated from an HIV-positive patient, was demonstrated to belong to the new B0/N-90 group. A primer set for PCR detection of B0/N-90 lineage-specific mutations has been developed. The prospective use of mce3 mutant genes as genetically engineered vaccine is discussed.

Comparative genomics and association analysis identifies virulence genes of Cercospora sojina in soybean

“…Non-synonymous SNPs can be used for the detection of new fungal groups with potentially changed phenotypes, including drug resistance, increased virulence levels, and pathogenicity, all of which can influence disease severity [45]. This diversity is created by mutations affecting gene product structure and function [46][47][48].…”

Comparative Genomics and Association Analysis Identifies Virulence Genes of Cercospora sojina on Soybean

“…Mutations of this enzyme in different varieties affects the activity of the enzyme, and thus, host resistance [42]. A05375 was speculated as NRPS8, which has been studied in Aspergillus fumigatus and is metabolized in its Non-synonymous SNPs can be used for the detection of new fungal groups with potentially changed phenotypes, including drug resistance, increased virulence levels, and pathogenicity, all of which can influence disease severity [45]. This diversity is created by mutations affecting gene product structure and function [46][47][48].…”

Development of a technological platfom for creating innovative anti-tb drugs effective against multi-drug-resistant strains

“…• отбор соединений, способных поражать 2 -3 биомишени M. tuberculosis, в том числе белки вирулентности [5,6,12].…”

“…Они агрессивно захватывают всё новые территории и представляют опасность прежде всего для групп населения с пониженным иммунитетом, в том числе для детей. Как правило, все эти эпидемиологически опасные сублинии характеризуются МЛУ/ШЛУ устойчивостью [5,6]. Увеличение числа случаев потери трудоспособности и рост смертности в связи с быстрым распространением МЛУ/ШЛУ возбудителя туберкулёза и угрозами, которые он несёт для групп населения с пониженным иммунитетом, в скором будущем могут стать социально опасным явлением.…”