Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil

Abstract

BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drugresistant TB (XDR-TB) has increased considerably worldwide.OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution.METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB).FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONSThe present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.

A precision overview of genomic resistance screening in Ecuadorian isolates of Mycobacterium tuberculosis using web-based bioinformatics tools

“…In our study, we analysed the rrs gene and identified several substitutions associated with streptomycin (positions 514, 517, 888, and 906) or linked to cross-resistance to kanamycin, capreomycin, or amikacin (1401A>G). It is worth noting that this mutation has been found to confer high levels of resistance in previous studies [8,72,[88][89][90][91][92]. Moreover, our study identified two isolates with the -12C>T mutation in the eis promoter that have been associated with low-level kanamycin resistance, supporting previous research findings [93,94].…”

A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools

“…A high proportion of STR resistance was observed in this study, which 60.7% of mutations was in the rpsL gene, agreeing that the k43R mutation is the most recurrent streptomycin resistance-associated mutation (32,79,81). In the rrs gene, the substitutions identified at positions 492, 514, 517, 888 and 906 previously have been associated with streptomycin resistance in TB (8,62,82,83); even though the 1401A>G, 1402C>T, and 1484G>T have been associated with cross-resistance to kanamycin, capreomycin or amikacin (84)(85)(86), only 1401A>G mutation was presented in 7.1% of isolates.…”

Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019

“…Several recent studies have examined the contribution of katG and inhA promoter mutations in drug-resistant TB isolates, and the results revealed significant geographic diversity across regions [ 25 – 27 ]. This study found that the most common mutation of MDR-TB was 34.7% (Ser531 → Leu + Ser315 → Thr), however, a study in Brazil showed that was 41.7% [ 28 ]. In our study, the mutation rate in katG 315 was 71.9%, which was higher than the mutation rates reported in Poland (66.0%) and Hebei Province, China (69.9%) [ 29 , 30 ].…”