Genomic analysis of the emergence of drug-resistant strains of Mycobacterium tuberculosis in the Middle East

Abstract

Tuberculosis (TB) represents a significant challenge to public health authorities, especially with the emergence of drug-resistant (DR) and multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis. We sought to examine the genomic variations among recently isolated strains of M. tuberculosis in two closely related countries with different population demography in the Middle East. Clinical isolates of M. tuberculosis from both Egypt and Saudi Arabia were subjected to phenotypic and genotypic analysis on gene and genome-wide levels. Isolates with MDR phenotypes were highly prevalent in Egypt (up to 35%) despite its relatively stable population structure (sympatric pattern). MDR-TB isolates were not identified in the isolates from Saudi Arabia despite its active guest worker program (allopatric pattern). However, tuberculosis isolates from Saudi Arabia, where lineage 4 was more prevalent (>65%), showed more diversity than isolates from Egypt, where lineage 3 was the most prevalent (>75%). Phylogenetic and molecular dating analyses indicated that lineages from Egypt were recently diverged (~78 years), whereas those from Saudi Arabia were diverged by over 200 years. Interestingly, DR isolates did not appear to cluster together or spread more widely than drug-sensitive isolates, suggesting poor treatment as the main cause for emergence of drug resistance rather than more virulence or more capacity to persist.

Low-Level Rifampin Resistance and rpoB Mutations in Mycobacterium tuberculosis: an Analysis of Whole-Genome Sequencing and Drug Susceptibility Test Data in New York

“…This link between compensatory mutations and strains with rpoB Ser450Leu has been well established (23,25,54,(57)(58)(59)(60). A majority of rpoC mutations identified in our study have been described in previous reports (54,(57)(58)(59)(60)(61)(62)(63)(64)(65)(66). Many of these mutations are located between codons 431 and 527, a particular region identified as harboring mutations that may compensate for the fitness cost of rpoB resistance mutations (53).…”

Fingerprinting of Mycobacterium tuberculosis isolates by MIRU-VNTR genotyping and detection of isoniazid resistance by real-time PCR

“…In contrast to those previous studies from Egypt [59][60][61][62], the majority of our isolates (26/50, 52 %) belonged to the S family of lineage_4 (Euro-American). Interestingly, another Arabian study conducted among Egyptian and Saudi Arabian patients [63] stated that lineage_3 was the most prevalent (>75 %) among their Egyptian isolates.…”

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

“…This finding also illustrated that the TB structure in a country is likely to be influenced by TB events in the neighboring countries in addition to local factors. Therefore, regional coordination in TB control is cardinal as movements of people for trade, migration, and refuge facilitate the spread of TB [ 39 , 40 ]. SIT21/CAS1-Kili (L3.1.1) strains related to the Zambian and other African countries are also causing TB disease in European countries such as the United Kingdom, as suggested by the existence of these strains in the same clade.…”