scholarly journals Mutations inside rifampicin-resistance determining region of rpoB gene associated with rifampicin-resistance in Mycobacterium tuberculosis

2018 ◽  
Vol 11 (5) ◽  
pp. 605-610 ◽  
Author(s):  
Myo T. Zaw ◽  
Nor A. Emran ◽  
Zaw Lin
2020 ◽  
Vol 20 (4) ◽  
pp. 491-494 ◽  
Author(s):  
Eltayib H. Ahmed Abakur ◽  
Tarig M.S. Alnour ◽  
Faisel Abuduhier ◽  
Fahad M.A. Albalawi ◽  
Khalid A.S. Alfifi

Purpose: Heteroresistant Mycobacterium tuberculosis (MTB) is defined as a group of drug-susceptible and resistant bacteria in a single clinical specimen from tuberculosis (TB) patients. Heteroresistance of MTB is considered a preliminary stage to full resistance. The present study aimed to determine the heteroresistance in Mycobacterium tuberculosis in Tabuk province, in the north of the Kingdom of Saudi Arabia. Method: GenoType MTBDRplus assay was used to determine mutations associated with isoniazid and rifampicin resistance. Results: A total number of 46 confirmed M. tuberculosis positive sputum samples were scanned for heteroresistance. The present study revealed 3 (6.5%) heteroresistant mutations to either rpoB gene alone, 2 (4.4%) to rpoB and 1 (2.2%) to inhA genes. Conclusion: The detection of heteroresistant mutations could guide the initiation of an appropriate regimen of treatment.


2020 ◽  
Vol 17 (2) ◽  
pp. 0444
Author(s):  
Fairuz Tawgozy et al.

Mycobacterium tuberculosis resistance to rifampicin is mainly mediated through mutations in the rpoB gene. The effects of rpoB mutations are relieved by secondary mutations in rpoA or rpoC genes. This study aims to identify mutations in rpoB, rpoA, and rpoC genes of Mycobacterium tuberculosis isolates and clarify their contribution to rifampicin resistance. Seventy isolates were identified by acid-fast bacilli smear, Genexpert assay, and growth on Lowenstein Jensen medium. Drug susceptibility, testing was performed by the proportional method.  DNA extraction, PCR, and sequencing were accomplished for the entire rpoA, rpoB, and rpoC genes. Twenty-three isolates (32.85%) showed resistance to rifampicin by either proportion method or Genexpert assay. Sequence analysis of the rpoB gene revealed fourteen different mutation patterns. Inside the rifampicin resistance determining region (RRDR), codons: S531L, D516V were highly mutated with frequencies of (21.73%, 17.39%) respectively. Outside the RRDR, there were nine different types of mutations, and M479L was the most prevalent one. Out of 23 RIF resistant isolates, seven isolates (30.43%) carried mutations in the rpoA gene, and twelve isolates (52.17%) harbored a mutation in rpoC. Most of the mutations were identified for the first time in this study. The current study demonstrated that mutations in rpoB, rpoA, and rpoC contributed to RIF resistance in Mycobacterium tuberculosis and this new finding may be relevant to realize how compensatory mutations in the rpoA and rpoC genes restore the fitness cost caused by rifampin resistance-conferring mutations in rpoB.


2020 ◽  
Vol 3 ◽  
pp. e11
Author(s):  
Victor Omote ◽  
◽  
Henry Awele Ukwamedua ◽  
Henry Uzor Oshilonya ◽  
Nathaniel Bini ◽  
...  

The emergence and spread of multi-drug resistant-tuberculosis is a threat, which has complicated the diagnosis, management and control of tuberculosis. In addition to the simultaneous detection of Mycobacterium tuberculosis bacilli and rifampicin resistance, the Gene Xpert assay can also highlight the point of mutation if it occurs around the rifampicin resistance determination region (RRDR) of the rpoB gene, which is responsible for 95% of rifampicin resistance. This study seeks to estimate the prevalence of rifampicin resistance, determine the frequency and distribution of mutations along the rifampicin resistance determination region, and assay for the relationship that exists between these mutations and basic epidemiological variables.


Author(s):  
Tarsizio Chikaonda ◽  
Irene Ketseoglou ◽  
Nelson Nguluwe ◽  
Robert Krysiak ◽  
Isaac Thengolose ◽  
...  

Background: Availability and access to the detection of resistance to anti-tuberculosis drug sremains a significant challenge in Malawi due to limited diagnostic services. The Xpert® MTB/RIF can detect Mycobacterium tuberculosis and resistance to rifampicin in a single, rapid assay. Rifampicin-resistant M. tuberculosis has not been well studied in Malawi.Objectives: We aimed to determine mutations in the rifampicin resistance determining region (RRDR) of the rpoB gene of M. tuberculosis strains which were defined as resistant to rifampicin by the Xpert MTB/RIF assay.Methods: Rifampicin-resistant isolates from 43 adult patients (≥ 18 years) from various districts of Malawi were characterised for mutations in the RRDR (codons 507–533) of the rpoB gene by DNA sequencing.Results: Mutations were found in 37/43 (86%) of the resistant isolates in codons 511, 512, 513,516, 522, 526 and 531. The most common mutations were in codons 526 (38%), 531 (29.7%) and 516 (16.2%). Mutations were not found in 6/43 (14%) of the resistant isolates. No novel rpoB mutations other than those previously described were found among the rifampicin-resistant M. tuberculosis complex strains.Conclusion: This study is the first to characterise rifampicin resistance in Malawi. The chaintermination DNA sequencing employed in this study is a standard method for the determination of nucleotide sequences and can be used to confirm rifampicin resistance obtained using other assays, including the Xpert MTB/RIF. Further molecular cluster analysis, such as spoligotyping and DNA finger printing, is still required to determine transmission dynamics and the epidemiological link of the mutated strains.


Author(s):  
Poonam Sharma ◽  
Rambir Singh

Introduction: Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) continues to be one of the most significant causes of death in the developing countries. Development of Multi Drug Resistance (MDR) and Extremely Drug Resistance (XDR) strains of MTB has been recognised as a major threat. Rapid diagnosis along with drug sensitivity analysis is the prerequisite for effective treatment of TB, especially in rural and remote location settings. Aim: The goal of this study was to investigate the Rifampicin Resistance (RR) using GeneXpert MTB/Rifampicin (RIF) in tribal patients suffering from Pulmonary Tuberculosis (PTB) in District Anuppur, Madhya Pradesh, India. Materials and Methods: Sputum samples were obtained from 413 patients with symptoms of PTB, who visited District Hospital, Anuppur from April 2017- April 2018. Based on clinical symptoms and chest X-ray, GeneXpert MTB/RIF assay was performed for the confirmation of TB and detection of RR. The data was analysed and expressed in percentage. Results: Out of 413 samples, 104 (25.18%) were diagnosed with PTB. Out of 104 TB positive samples, RR was detected in 7(6.73%) samples. The most common mutations conferring RR were located in the region of Probe B (71.42%), followed by Probe C (14.28%) and Probe E (14.28%), while no mutations were found in the region of Probe A and Probe D. Conclusion: Possibly, this is the first report of RR and probe mutational analysis from this tribal region of India. High rate of mutation at Probe B locus may be the chief reason for RR development. Gene sequencing may be carried for understanding the higher rates of mutations at probe B locus.


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