Whole genomic sequencing based genotyping reveals a specific X3 sublineage restricted to Mexico and related with multidrug resistance

Abstract

Whole genome sequencing (WGS) has been shown to be superior to traditional procedures of genotyping in tuberculosis (TB), nevertheless, reports of its use in drug resistant TB (DR-TB) isolates circulating in Mexico, are practically unknown. Considering the above the main of this work was to identify and characterize the lineages and genomic transmission clusters present in 67 DR-TB isolates circulating in southeastern Mexico. The results show the presence of three major lineages: L1 (3%), L2 (3%) and L4 (94%), the last one included 16 sublineages. Sublineage 4.1.1.3 (X3) was predominant in 18 (27%) of the isolates, including one genomic cluster, formed by eleven multidrug resistant isolates and sharing the SIT 3278, which seems to be restricted to Mexico. By the use of WGS, it was possible to identify the high prevalence of L4 and a high number of sublineages circulating in the region, also was recognized the presence of a novel X3 sublineage, formed exclusively by multidrug resistant isolates and with restrictive circulation in Mexico for at least the past 17 years.

Mycobacterial Lineages Associated with Drug Resistance in Patients with Extrapulmonary Tuberculosis in Addis Ababa, Ethiopia

“…However, we were unable to compare our data to that of other studies in the country because there was no data on pre-XDR/XDR Mycobacterium tuberculosis resistance isolates in combination with EPTB genotypes. However, the finding is in agreement with a previous investigation in Mexico where the Euro-American lineage was predominantly identified among the pre-XDR/XDR Mycobacterium tuberculosis isolates [ 38 ]. More importantly, the higher prevalence rate of MDR-TB strains with additional resistance to the second-line anti-TB drugs in this study warrants the urgent need for reinforcement of the TB control program [ 28 ].…”

Genomics epidemiology analysis reveals hidden signatures of drug resistance in Mycobacterium tuberculosis

“…Interestingly, we identified seven isolates (distributed in the north: Nuevo Leon, Zacatecas, San Luis Potosi; center: State of Mexico; and south: Chiapas) belonging to the X-type (4.1.1.3), an endemic sublineage recently reported in Veracruz and Guadalajara (18, 19) that has been strongly associated with drug-resistance (46). Three of these samples (43%) showed phenotypic drug-resistant profiles (EZ, HZ, and HRSZ, respectively).…”

Whole genome characterization, and geographical distribution of M. tuberculosis in central region of Veracruz, Mexico

“…1 Multidrug- (MDR-TB) and extensively drug resistant-tuberculosis (XDR-TB) have been increasing annually, placing Mexico among the five main TB contributors in the Americas. 5 Unfortunately there are few studies related to the characterization of TB in Mexico, using WGS, 6 , 7 thus limiting the evaluation of its effectiveness. Considering the above, this study aimed to use WGS to characterize the M. tuberculosis isolates circulating in the central region of the state of Veracruz, Mexico, and by use of geographic information system determine the geographic distribution of the lineages found.…”

“… 13 Phylogeny and genomic clusters were determined following recommendations by Jimenez-Ruano et al. 7 and final tree visualization was done with Ito. 14 Calculation of pairwise genetic distances between isolates considered a ≤ 12 SNPs threshold, as recommend Walker et al.…”

“…The isolates analyzed were placed in seven L4 sublineages, which have been previously described as predominant in Mexico, 6 , 7 and Latin America, and explained by historical events related with European colonization, and further migration of population in the continent. 18 , 19 …”