Comparative genomics of drug-resistant strains of Mycobacterium tuberculosis in Ecuador

Abstract

Background Tuberculosis is a serious infectious disease affecting millions of people. In spite of efforts to reduce the disease, increasing antibiotic resistance has contributed to persist in the top 10 causes of death worldwide. In fact, the increased cases of multi (MDR) and extreme drug resistance (XDR) worldwide remains the main challenge for tuberculosis control. Whole genome sequencing is a powerful tool for predicting drug resistance-related variants, studying lineages, tracking transmission, and defining outbreaks. This study presents the identification and characterization of resistant clinical isolates of Mycobacterium tuberculosis including a phylogenetic and molecular resistance profile study by sequencing the complete genome of 24 strains from different provinces of Ecuador. Results Genomic sequencing was used to identify the variants causing resistance. A total of 15/21 isolates were identified as MDR, 4/21 as pre-XDR and 2/21 as XDR, with three isolates discarded due to low quality; the main sub-lineage was LAM (61.9%) and Haarlem (19%) but clades X, T and S were identified. Of the six pre-XDR and XDR strains, it is noteworthy that five come from females; four come from the LAM sub-lineage and two correspond to the X-class sub-lineage. A core genome of 3,750 genes, distributed in 295 subsystems, was determined. Among these, 64 proteins related to virulence and implicated in the pathogenicity of M. tuberculosis and 66 possible pharmacological targets stand out. Most variants result in nonsynonymous amino acid changes and the most frequent genotypes were identified as conferring resistance to rifampicin, isoniazid, ethambutol, para-aminosalicylic acid and streptomycin. However, an increase in the resistance to fluoroquinolones was detected. Conclusion This work shows for the first time the variability of circulating resistant strains between men and women in Ecuador, highlighting the usefulness of genomic sequencing for the identification of emerging resistance. In this regard, we found an increase in fluoroquinolone resistance. Further sampling effort is needed to determine the total variability and associations with the metadata obtained to generate better health policies.

A first insight into tuberculosis transmission at the border of Ecuador and Colombia: a retrospective study of the population structure of Mycobacterium tuberculosis in Esmeraldas province

“…There is a single study addressing the population structure and genetic diversity of MTBC in the whole country, showing that MTBC lineage 4 sublineage LAM is predominant countrywide, and sublineages X and S are also predominant in the Coastal and Andean regions, respectively ( 9 ). Similar results have been reported in other studies with MTBC strains from Quito ( 10 ) and Guayaquil ( 12 ).…”

“…For 2021, the World Health Organization (WHO) estimated for Ecuador a burden of 8500 TB cases (rate of 48/100,000 population) and 370 cases of multidrug resistance TB (MDR-TB) (rate 2.1 of 100,000 population), 830 deaths of HIV-negative TB patients and 330 deaths of HIV-positive TB patients (TB case fatality ratio: 14%) (8). MTBC molecular epidemiology studies in Ecuador are really scarce (9)(10)(11)(12). There is a single study addressing the population structure and genetic diversity of MTBC in the whole country, showing that MTBC lineage 4 sublineage LAM is predominant countrywide, and sublineages X and S are also predominant in the Coastal and Andean regions, respectively (9).…”

Investigating the Mutations in atpE and Rv0678 Genes in Mycobacterium Tuberculosis Clinical Isolates

“…In our study, MDR and XDR rates were 72.2% and 27.8%, respectively, which agree with those reported by Mansoor et al (2023), highlighting a similar distribution of drug-resistant tuberculosis [22]. In Ecuador, among 21 isolates investigated in 2023, 15 (71.4%) were MDR, and 2 (9.5%) were XDR, rates that almost match our findings [23]. In a 2023 study in India, of 64 isolates, 43 (67.1%) were identified as MDR and 2 (3.1%) as XDR [24].…”