Mycobacterium kansasii is a nontuberculous mycobacterium that can cause serious pulmonary disease. Genotyping suggested that the species is composed of at least six subtypes that vary in clinical significance, with subtype I being clinically dominant but less commonly isolated from environmental sources. Here we report a population genomics study of 358 M. kansasii isolates obtained from global water and clinical sources. Phylogenomic analyses revealed that the six subtypes are more accurately designated as closely related subspecies. These subspecies show ample evidence of recombination mediated by distributive conjugative transfer that has contributed to subspeciation and on-going diversification. Water was confirmed as a source of clinical infections by showing that genomes of clinical strains from an Australian outbreak were almost indistinguishable from strains contaminating the drinking water supply. Most clinical infections (nearly 80%) were due to a recently emerged group of strains designated the M. kansasii main complex (MKMC), which appears to have originated in Europe in 1900s and expanded globally over the past century. Comparative genomic analyses revealed that the MKMC has maintained the methylcitrate cycle and expanded ESX-I secretion-associated proteins, perhaps facilitating metabolic adaptation and pathogenicity for human hosts. Evidence of on-going positive selection in isolates of the MKMC was found in genes involved in carbon and secondary metabolism, metal ion homeostasis and cell surface remodeling that could represent adaptation to human hosts. These results further our understanding of the epidemiology and pathogenicity of M. kansasii and emphasize the importance of monitoring its potential transition to a more human-adapted pathogen.
BACKGROUND Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB), remains a severe public health problem globally. Guizhou has the fourth highest TB report rate of pulmonary TB around China. Uncovering the current status of TB epidemic, and distinguishing disease caused by recent or remote infections are the key issue to formulate effective prevention and control strategy. However, these data are limited in Guizhou. In this study, we aimed to investigate the transmission and drug-resistance profiles of TB in Luodian, a highest TB incidence and resources limited area in Guizhou, China. METHODS During 22 May 2018 to 21 April 2019, individuals with positive MTB culture were enrolled, all of them accepted the standardized interview. MTB isolates were performed whole genome sequencing. The prevalence of MTB genotypes, the genomic cluster rate and drug-resistance conferring mutations were analyzed based on the sequencing data. RESULTS A total of 107 cases were enrolled, of which 64.5% were male, and the median age of the patients was 51 years old (interquartile range, 40–65 years old). 84% patient were new case while 16% were retreated cases. All cases excepted three came from nine towns, and 55.1% of cases were from Longping and Bianyang. The phylogeny tree showed that 53.3% of strains were Lineage 2 (Beijing genotype), while 46.7% were Lineage 4 (Euro-American genotype). Among Lineage 2 strains, 66.7% were modern Beijing. Seven clusters with genomic distance within 12 SNVs were identified. The clusters included 14 strains, accounting for a cluster rate of 13.1%. The distance of clustered cases was between 2.1 to 71 kilometers (Km), with a media distance of 14 Km (interquartile range, 2.8–38 Km). Cases of two clusters came from the same town. Based on the gene mutations associated to drug-resistance, we predicted that 4.8% was resistant to isoniazid, 3.7% to rifampicin, 3.7% to streptomycin, and only one strain (0.9%) was multidrug resistance (MDR). CONLUSIONS: The study found high transmission and low drug-resistance rate in Luodian, and sublineages of modern Beijing branch had recent expansion in Luodian. this work also may serve as a genomic baseline to study the evolution and spread of MTB in Guizhou.
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