MEX-TB, genomic epidemiology of Mycobacterium tuberculosis strains from Mexico

Mexico ranks third among the main contributors of Tuberculosis (TB) in the Americas. Unlike other countries, very few Whole Genome Sequences (WGS) of Mycobacterium tuberculosis strains have been obtained and analyzed in this region. Here, we obtain the WGS of 53 M. tuberculosis isolates derived from TB-positive patients from 17 states in Mexico, collected between 1998 and 2019. Patient metadata on gender, age, location, TB-associated risk factors, and comorbidities were retrieved. The classification of sublineages and the identification of transmission groups was achieved with the MTBseq tool. We found that 98% of our samples belonged to the Euro-American Lineage (L4), featuring a similar distribution of sublineages X-type (33.08%), LAM (22.56%) and Haarlem (21.05%). In addition, drug susceptibility to isoniazid, rifampin, ethambutol, streptomycin, and pyrazinamide was tested using the BACTEC MGIT 960 fluorimetric method for all M. tuberculosis samples. The results indicated that 19% of our samples were multidrug resistant (MDR). Genome-scale drug resistance genotyping was achieved with the TBprofiler tool. The strength of agreement between the phenotypic and genotypic profiles of drug resistance was determined using Cohen's kappa coefficient (k). We found several discrepancies for all tested antibiotics based on their k values. Additionally, we performed a functional analysis of non-canonical variants present in M. tuberculosis samples displaying drug resistance phenotypes by using a newly designed bioinformatic tool, named FuN-TB. We found several genes containing mutations that may be involved in the drug resistance phenotypes exhibited by certain strains of M. tuberculosis from Mexico.