Mutations Associated with Rifampicin Resistance in Mycobacterium tuberculosis Isolates from Moroccan Patients: Systematic Review

Abstract

Background. In recent years, the treatment of tuberculosis has been threatened by the increasing number of patients with drug resistance, especially rifampicin resistance, which is the most effective first-line antibiotic against Mycobacterium tuberculosis. Methods. We performed a systematic review of the literature by searching the PubMed database for studies of rifampicin-resistant Mycobacterium tuberculosis (MTB) isolates from Moroccan patients, published between 2010 and 2020. The aim of this review was to quantify the frequency of the most common mutations associated with rifampicin resistance, to describe the frequency at which these mutations co-occur. Identified studies were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Results. 6 studies met our inclusion criteria. Results show that 99.36% of MTB isolates had a single-point mutation, and the most commonly mutated codon of rpoB gene is 531 with 70.33% of phenotypically resistant strains. However, 10.38% of MTB strains phenotypically resistant to RIF did not exhibit any mutation in the rpoB gene. Conclusion. Identification of a resistance-associated mutation to rifampicin can be a good marker of drug-resistant TB, but lack of a mutation in the target sequence must be interpreted with caution.

Prevalence and Molecular Characteristics Based on Whole Genome Sequencing of Mycobacterium tuberculosis Resistant to Four Anti-Tuberculosis Drugs from Southern Xinjiang, China

“…[5][6][7][8][9] Mutations in RMP resistant determined region (RRDR) of rpoB is the major cause for RMP resistance, with codons 450, 445 and 435 being the predominant sites. 10 INH resistance is mainly related to the mutations in katG, followed by that in the inhA promoter and oxyR-ahpC intergenic region. 11 Mutations in rpoB and katG were found attributed to 91.1-97.7% RMP resistance 5,12 and 65-88.5% INH resistance, 13,14 respectively.…”

The Epistatic Landscape of Antibiotic Resistance of Different Clades of Mycobacterium tuberculosis

“…The evolution of antibiotic resistance started from a mutation in codon 55 in a putative dehydrogenase/reductase Rv1928c whose involvement in INH resistance was hypothesized in a recent paper [56]. This mutation made it possible for several other DR mutations to occur independently from each other: rpoB:496 for RIF resistance [57], dnaA:233 for INH resistance [58], ethA:59 for ethionamide resistance [59], embB:306 for EMB resistance [60] and pncA:68 for pyrazinamide [61]. The mutation Rv1928c:55 was a prerequisite for many other subordinate mutations, particularly in murA encoding a key enzyme of peptidoglycan biosynthesis, polyketide synthase pks17 and desA3 predicted as a potential DR gene [56].…”

Frequency of rpoB, katG, and inhA Gene Polymorphisms Associated with Multidrug-Resistant Mycobacterium tuberculosis Complex Isolates among Ethiopian TB Patients: A Systematic Review

“…Early case detection and treatment of MDR/XDR-TB cases is essential to prevent and control the transmission of TB [ 6 ], and has become an urgent public health problem in developing countries including Ethiopia, due to their complex diagnostic and treatment obstacles [ 7 ]. Some of the significant factors associated with increasing the development of drug-resistant tuberculosis (DR-TB) and the risk of direct transmission of DR-TB are an increase of TB with HIV-1 co-infection, overcrowded living conditions, lack of or poor access to healthcare such as lack of DR-TB diagnostic tools and delaying drug susceptibility testing (DST) practices, inadequate administration of anti-TB therapy regimens with inappropriate prescription of anti-TB drugs and patient compliance [ 8 ], weak TB prevention and control program, and high prevalence of diabetes mellitus, alcoholism, and smoking [ 9 , 10 ]. It has been recognized as a poverty-related disease.…”

“…Multiple reviews have identified genes that encode drug targets and have summarized the various mechanisms of resistance to both INH and RIF [ 14 , 15 ]. Moreover, greater than 95% of RIF resistance is associated with mutations in an 81 base pair section of the rpoB gene, while INH resistance appears more complex and has been associated with multiple genes, most frequently katG gene and inhA promoter region [ 8 , 16 – 18 ].…”

“…RIF is one of the most potent first-line anti-TB drugs and has very effective bactericidal activity against MTBC during TB treatment. Resistance to RIF is the most important indicator of MDR-TB and serves as a surrogate marker for the detection of MDR-TB [ 8 ]. The primary mechanism of RIF resistance is due to the mutations in the rpoB gene that encode the DNA-dependent RNA polymerase β -subunit [ 19 , 20 ].…”