Genome-wide analysis of drug resistant Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in Russia

Mycobacterium tuberculosis is a highly studied pathogen due to public health importance. Despite progress in M.tuberculosis genome diversity analysis there remain insufficient data on genome analysis of M.tuberculosis strains associated with pulmonary vs. extrapulmonary TB (PTB or XPTB respectively) tissue localization. Here we conduct comparative analysis of whole-genome sequence (WGS) for clinical M.tuberculosis strains collected from patients with PTB (n=72) and XPTB (n=73) localization. We further analyze the incidence of point mutations widely used for drug resistance detection in laboratory practice.\n\nM.tuberculosis isolates were collected from patients with varying clinical status from 2007 to 2014 in Russia. Bacterial DNA was extracted and sequenced using MiSeq platform (Illumina).\n\nWGS data allowed identifying M.tuberculosis substrains associated with distinctions in the occurrence in PTB v s. XPTB cases. There occurred little statistically significant specific DNA variants or genotypes diagnostic of tissue distribution, however phylogenetic analyses did reveal M.tuberculosis genetic substrains associated with TB localization. XPTB was associated with Beijing CAO, A and 4.8 groups, while PTB localization was associated with group LAM (4.3). Further, XPTB strain in some cases showed elevated drug resistance patterns relative to PTB isolates. HIV is significantly associated with the development of XPTB in the Beijing B0/W148 group and among unclustered Beijing isolates.\n\nThis research analysis pinpointed genomic markers identified in XPTB and PTB with detailed characterization of drug-resistance markers of Russian M.tuberculosis isolates. We suggest that further comprehensive analysis of bacterial and human biological signatures might allow for better understanding consistent pattern of XPTB development.\n\nSummaryThis paper gives genome-wide characteristics of Mycobacterium tuberculosis strains collected from pulmonary and extrapulmonary tuberculosis patients:\n\n- M.tuberculosis genetic strains associated with TB tissue localization,\n\n- influence of HIV co-infection on TB dissemination;\n\n- mutations associated with M.tuberculosis drug resistance.