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.

scholarly journals Automatic Identification of Individual rpoB Gene Mutations Responsible for Rifampin Resistance in Mycobacterium tuberculosis by Use of Melting Temperature Signatures Generated by the Xpert MTB/RIF Ultra Assay

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Yuan Cao ◽  
Heta Parmar ◽  
Ann Marie Simmons ◽  
Devika Kale ◽  
Kristy Tong ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Melting Temperature ◽  
Gene Mutations ◽  
Test Sample ◽  
Rpob Gene ◽  
Automatic Identification ◽  
Content Type ◽  
Automated Algorithm ◽  
Wide Range ◽  
Rifampin Resistance

ABSTRACT Molecular surveillance of rifampin-resistant Mycobacterium tuberculosis can help to monitor the transmission of the disease. The Xpert MTB/RIF Ultra assay detects mutations in the rifampin resistance-determining region (RRDR) of the rpoB gene by the use of melting temperature (Tm) information from 4 rpoB probes which can fall in one of the 9 different assay-specified Tm windows. The large amount of Tm data generated by the assay offers the possibility of an RRDR genotyping approach more accessible than whole-genome sequencing. In this study, we developed an automated algorithm to specifically identify a wide range of mutations in the rpoB RRDR by utilizing the pattern of the Tm of the 4 probes within the 9 windows generated by the Ultra assay. The algorithm builds a RRDR mutation-specific “Tm signature” reference library from a set of known mutations and then identifies the RRDR genotype of an unknown sample by measuring the Tm distances between the test sample and the reference Tm values. Validated using a set of clinical isolates, the algorithm correctly identified RRDR genotypes of 93% samples with a wide range of rpoB single and double mutations. Our analytical approach showed a great potential for fast RRDR mutation identification and may also be used as a stand-alone method for ruling out relapse or transmission between patients. The algorithm can be further modified and optimized for higher accuracy as more Ultra data become available.

scholarly journals Resistance Levels and rpoB Gene Mutations among In Vitro-Selected Rifampin-Resistant Mycobacterium tuberculosis Mutants

2006 ◽  
Vol 50 (8) ◽  
pp. 2860-2862 ◽  
Author(s):  
Emma Huitric ◽  
Jim Werngren ◽  
Pontus Juréen ◽  
Sven Hoffner
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Point Mutations ◽  
Gene Mutations ◽  
Rpob Gene ◽  
Clinical Isolates ◽  
Large Deletions ◽  
High Level ◽  
Level Resistance

ABSTRACT The distribution and resistance levels of 189 in vitro-selected rifampin-resistant Mycobacterium tuberculosis mutants of Beijing and other genotypes were determined. Apart from a higher amount of codon 522 point mutations and large deletions, a spread of mutations similar to that reported for clinical isolates was seen. Most mutations were correlated with high-level resistance; a lower level, or a MIC of <16 mg/liter, was associated with codon 522 mutations. Multiple mutations were detected in two Beijing mutants.

Analysis of RNA Polymerase Beta Subunit (rpoB) Gene Sequences for the Discriminative Power of Marine Vibrio Species

2009 ◽  
Vol 58 (4) ◽  
pp. 679-691 ◽  
Author(s):  
Jang-Seu Ki ◽  
Rui Zhang ◽  
Wen Zhang ◽  
Yi-Li Huang ◽  
Pei-Yuan Qian
Keyword(s):  
Rna Polymerase ◽  
Rpob Gene ◽  
Vibrio Species ◽  
Beta Subunit ◽  
Discriminative Power ◽  
Gene Sequences ◽  
Polymerase Beta ◽  
Marine Vibrio

scholarly journals Autogenous regulation of RNA polymerase beta subunit synthesis in vitro

1978 ◽  
Vol 253 (13) ◽  
pp. 4501-4504
Author(s):  
R. Fukuda ◽  
M. Taketo ◽  
A. Ishihama
Keyword(s):  
Rna Polymerase ◽  
Beta Subunit ◽  
Polymerase Beta ◽  
Autogenous Regulation

scholarly journals Rapid Detection of rpoB Gene Mutations Conferring Rifampin Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 50 (7) ◽  
pp. 2433-2440 ◽  
Author(s):  
W. Ao ◽  
S. Aldous ◽  
E. Woodruff ◽  
B. Hicke ◽  
L. Rea ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Rapid Detection ◽  
Gene Mutations ◽  
Rpob Gene ◽  
Rifampin Resistance

scholarly journals Allelic Exchange and Mutant Selection Demonstrate that Common Clinical embCAB Gene Mutations Only Modestly Increase Resistance to Ethambutol in Mycobacterium tuberculosis

2009 ◽  
Vol 54 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Hassan Safi ◽  
Robert D. Fleischmann ◽  
Scott N. Peterson ◽  
Marcus B. Jones ◽  
Behnam Jarrahi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
In Vitro Selection ◽  
Gene Mutations ◽  
Wild Type ◽  
Mutant Selection ◽  
Preferential Growth ◽  
Allelic Exchange ◽  
High Level ◽  
Isogenic Mutants

ABSTRACT Mutations within codon 306 of the Mycobacterium tuberculosis embB gene modestly increase ethambutol (EMB) MICs. To identify other causes of EMB resistance and to identify causes of high-level resistance, we generated EMB-resistant M. tuberculosis isolates in vitro and performed allelic exchange studies of embB codon 406 (embB406) and embB497 mutations. In vitro selection produced mutations already identified clinically in embB306, embB397, embB497, embB1024, and embC13, which result in EMB MICs of 8 or 14 μg/ml, 5 μg/ml, 12 μg/ml, 3 μg/ml, and 4 μg/ml, respectively, and mutations at embB320, embB324, and embB445, which have not been identified in clinical M. tuberculosis isolates and which result in EMB MICs of 8 μg/ml, 8 μg/ml, and 2 to 8 μg/ml, respectively. To definitively identify the effect of the common clinical embB497 and embB406 mutations on EMB susceptibility, we created a series of isogenic mutants, exchanging the wild-type embB497 CAG codon in EMB-susceptible M. tuberculosis strain 210 for the embB497 CGG codon and the wild-type embB406 GGC codon for either the embB406 GCC, embB406 TGC, embB406 TCC, or embB406 GAC codon. These new mutants showed 6-fold and 3- to 3.5-fold increases in the EMB MICs, respectively. In contrast to the embB306 mutants, the isogenic embB497 and embB406 mutants did not have preferential growth in the presence of isoniazid or rifampin (rifampicin) at their MICs. These results demonstrate that individual embCAB mutations confer low to moderate increases in EMB MICs. Discrepancies between the EMB MICs of laboratory mutants and clinical M. tuberculosis strains with identical mutations suggest that clinical EMB resistance is multigenic and that high-level EMB resistance requires mutations in currently unknown loci.

Sign in / Sign up

Export Citation Format

Share Document