scholarly journals Interaction of CarD with RNA Polymerase Mediates Mycobacterium tuberculosis Viability, Rifampin Resistance, and Pathogenesis

2012 ◽  
Vol 194 (20) ◽  
pp. 5621-5631 ◽  
Author(s):  
L. A. Weiss ◽  
P. G. Harrison ◽  
B. E. Nickels ◽  
M. S. Glickman ◽  
E. A. Campbell ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rna Polymerase ◽  
Rifampin Resistance

scholarly journals Comparative antimycobacterial activities of rifampin, rifapentine, and KRM-1648 against a collection of rifampin-resistant Mycobacterium tuberculosis isolates with known rpoB mutations.

1996 ◽  
Vol 40 (11) ◽  
pp. 2655-2657 ◽  
Author(s):  
S L Moghazeh ◽  
X Pan ◽  
T Arain ◽  
C K Stover ◽  
J M Musser ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rna Polymerase ◽  
Gene Mutations ◽  
Rpob Gene ◽  
Genetic Alterations ◽  
Beta Subunit ◽  
Polymerase Beta ◽  
Antimycobacterial Agents ◽  
Rifampin Resistance

A collection of 24 rifampin-resistant clinical isolates of Mycobacterium tuberculosis with characterized RNA polymerase beta-subunit (rpoB) gene mutations was tested against the antimycobacterial agents rifampin, rifapentine, and KRM-1648 to correlate levels of resistance with specific rpoB genotypes. The results indicate that KRM-1648 is more active in vitro than rifampin and rifapentine, and its ability to overcome rifampin resistance in strains with four different genetic alterations may prove to be useful in understanding structure-function relationships.

Synergistic Interplay of The Co-administration of Rifampin And Newly Developed Anti-TB Drug: Could It Be a Promising New Line of TB Therapy?

2018 ◽  
Vol 21 (6) ◽  
pp. 453-460 ◽  
Author(s):  
Clement Agoni ◽  
Pritika Ramharack ◽  
Mahmoud E.S. Soliman
Keyword(s):  
Crystal Structure ◽  
Mycobacterium Tuberculosis ◽  
Rna Polymerase ◽  
Conformational Dynamics ◽  
Interaction Network ◽  
Mutant Enzyme ◽  
Structural Mechanism ◽  
Residue Interaction ◽  
Ligand Interactions ◽  
Rifampin Resistance

Background: Rifampin resistance has dampened the existing efforts being made to control the global crisis of Tuberculosis and antimicrobial resistance in general. Previous studies that attempted to provide insights into the structural mechanism of Rifampin resistance did not utilize the X-ray crystal structure of Mycobacterium tuberculosis RNA polymerase due to its unavailability. Methods/Results: We provide an atomistic mechanism of Rifampin resistance in a single active site mutating Mycobacterium tuberculosis RNA polymerase, using a recently resolved crystal structure. We also unravel the structural interplay of this mutation upon co-binding of Rifampin with a novel inhibitor, D-AAP1. Mutation distorted the overall conformational landscape of Mycobacterium tuberculosis RNA polymerase, reduced binding affinity of Rifampin and shifted the overall residue interaction network of the enzyme upon binding of only Rifampin. Interestingly, co-binding with DAAP1, though impacted by the mutation, exhibited improved Rifampin binding interactions amidst a distorted residue interaction network. Conclusion: Findings offer vital conformational dynamics and structural mechanisms of mutant enzyme-single ligand and mutant enzyme-dual ligand interactions which could potentially shift the current therapeutic protocol of Tuberculosis infections.

scholarly journals Discordance between Xpert MTB/RIF Assay and Bactec MGIT 960 Culture System for Detection of Rifampin-Resistant Mycobacterium tuberculosis Isolates in a Country with a Low Tuberculosis (TB) Incidence

2015 ◽  
Vol 53 (4) ◽  
pp. 1351-1354 ◽  
Author(s):  
Eiman Mokaddas ◽  
Suhail Ahmad ◽  
Hanaa S. Eldeen ◽  
Noura Al-Mutairi
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Culture System ◽  
Content Type ◽  
Rifampin Resistance ◽  
Xpert Assay

Among 452 samples that were positive by the Xpert MTB/RIF (Xpert) assay and MGIT 960 system (MGIT), 440 and 10Mycobacterium tuberculosissamples were detected as rifampin susceptible and rifampin resistant, respectively. Two isolates that were rifampin susceptible by the MGIT system were rifampin resistant by the Xpert assay.rpoBsequencing identified a silent (CTG521TTG) mutation in one isolate and a missense (GAC516TAC) mutation in another. The detection of rifampin resistance is imperfect with both the Xpert assay and MGIT system. Any discordant rifampin resistance results should be confirmed by sequencing of therpoBgene.

scholarly journals Amplification Refractory Mutation System – Polymerase Chain Reaction for Rapid Detection of rpoB Gene Mutations in Mycobacterium tuberculosis

2017 ◽  
Vol 5 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Hemanta Kumari Chaudhary ◽  
Mitesh Shrestha ◽  
Prakash Chaudhary ◽  
Bal Hari Poudel
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rpob Gene ◽  
Amplification Refractory Mutation System ◽  
Chain Reaction ◽  
Arms Pcr ◽  
Mutation System ◽  
Mdr Tb ◽  
Total Dna ◽  
Polymerase Chain ◽  
Rifampin Resistance

Multidrug-resistant tuberculosis (MDR-TB) has become a serious worldwide threat including in Nepal. MDR-TB refers to the pathological condition whereby Mycobacterium tuberculosis becomes resistant to the first line of drug treatment i.e. rifampin and isoniazid. Resistance to rifampin (RIF) is mainly caused by the mutations in the rpoB gene which codes for the β-subunit of RNA polymerase. In this study, Amplification Refractory Mutation System – Polymerase Chain Reaction (ARMS – PCR) technique has been used to detect mutations in the rpoB gene of Mycobacterium tuberculosis. Total DNA samples of 34 phenotypic MDR-TB were subjected to ARMS – PCR using three different codon specific primers (516, 526 and 531). These three codons occupy large portion of total mutation responsible for rifampin resistance. Out of the total DNA samples, all were bearing mutation in at least one of the three codons mentioned. Of those bearing mutation, the highest number had mutation in codon 531 (97.05 %) followed by codon 516 (17.64 %) and finally in codon 526 (11.76%) respectively. Hence, ARMS – PCR may be used as an alternative diagnostic technique for detection of rifampin resistance in Mycobacterium tuberculosis strains, especially for a developing country like Nepal.Int. J. Appl. Sci. Biotechnol. Vol 5(1): 81-85

scholarly journals Implication from the predicted docked interaction of sigma H and exploration of its interaction with RNA polymerase in Mycobacterium tuberculosis

2015 ◽  
Vol 11 (6) ◽  
pp. 296-301 ◽  
Author(s):  
Aayatti Mallick Gupta ◽  
◽  
Simanti Bhattacharya ◽  
Angshuman Bagchi ◽  
Sukhendu Mandal ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rna Polymerase ◽  
Sigma H

scholarly journals Molecular Analysis of Codon 548 in therpoBGene Involved in Mycobacterium tuberculosis Resistance to Rifampin

2014 ◽  
Vol 59 (3) ◽  
pp. 1542-1548 ◽  
Author(s):  
Yu-Tze Horng ◽  
Wen-Yih Jeng ◽  
Yih-Yuan Chen ◽  
Che-Hung Liu ◽  
Horng-Yunn Dou ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Resistance ◽  
Drug Susceptibility ◽  
Content Type ◽  
Stable Hydrogen Bond ◽  
Resistance Patterns ◽  
Resistant Strains ◽  
Rifampin Resistance ◽  
Susceptibility Tests ◽  
Dna Complex

ABSTRACTMostMycobacterium tuberculosisrifampin-resistant strains have been associated with mutations in an 81-bp rifampin resistance-determining region (RRDR) in the generpoB. However, if this region alone were targeted, rifampin-resistant strains with mutations outside the RRDR would not be detected. In this study, among 51 rifampin-resistant clinical isolates analyzed by sequencing 1,681-bp-long DNA fragments containing the RRDR, 47 isolates contained mutations within the RRDR, three isolates contained mutations both within and outside the RRDR, and only one isolate had a single missense mutation (Arg548His) located outside the RRDR. A drug susceptibility test of recombinantMycobacterium smegmatisandM. tuberculosisisolates carrying mutatedrpoB(Arg548His) showed an increased MIC for rifampin compared to that of the control strains. Modeling of the Arg548His mutant RpoB-DNA complex revealed that the His548 side chain formed a more stable hydrogen bond structure than did Arg548, reducing the flexibility of the rifampin-resistant cluster II region of RpoB, suggesting that the RpoB Arg548His mutant does not effectively interact with rifampin and results in bacterial resistance to the drug. This is the first report on the relationship between the mutation in codon 548 of RpoB and rifampin resistance in tuberculosis. The novel mutational profile of therpoBgene described here will contribute to the comprehensive understanding of rifampin resistance patterns and to the development of a useful tool for simple and rapid drug susceptibility tests.

scholarly journals Rifampin Resistance in Mycobacterium kansasii Is Associated with rpoB Mutations

2001 ◽  
Vol 45 (11) ◽  
pp. 3056-3058 ◽  
Author(s):  
John L. Klein ◽  
Timothy J. Brown ◽  
Gary L. French
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Basis ◽  
Strong Association ◽  
Missense Mutations ◽  
Β Subunit ◽  
Mycobacterium Kansasii ◽  
Bacterial Rna ◽  
Rifampin Resistance ◽  
Potent Drug

ABSTRACT Rifampin is the most potent drug used in the treatment of disease due to Mycobacterium kansasii. A 69-bp fragment ofrpoB, the gene that encodes the β subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. This sequence showed 87% homology with the Mycobacterium tuberculosis gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin-resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determined by E-test were <1 mg/liter for all rifampin-susceptible isolates and >256 mg/liter for all rifampin-resistant ones. In addition, four of the five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between rpoB gene missense mutations and rifampin resistance in M. kansasii. Although our results are derived from a small number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.

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