scholarly journals High Frequency of Mutations in the rpoB Gene in Rifampin-Resistant Clinical Isolates of Mycobacterium tuberculosis from Singapore

2005 ◽  
Vol 43 (4) ◽  
pp. 2026-2027 ◽  
Author(s):  
A. S. G. Lee ◽  
I. H. K. Lim ◽  
L. L. H. Tang ◽  
S. Y. Wong
Keyword(s):  
Mycobacterium Tuberculosis ◽  
High Frequency ◽  
Rpob Gene ◽  
Clinical Isolates

scholarly journals Relationship between rifampin MICs for and rpoB mutations of Mycobacterium tuberculosis strains isolated in Japan.

1996 ◽  
Vol 40 (4) ◽  
pp. 1053-1056 ◽  
Author(s):  
H Ohno ◽  
H Koga ◽  
S Kohno ◽  
T Tashiro ◽  
K Hara
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Point Mutation ◽  
Rpob Gene ◽  
The Other ◽  
Clinical Isolates ◽  
Sequencing Analysis ◽  
The Relationship

We analyzed the relationship between rifampin MICs and rpoB mutations of 40 clinical isolates of Mycobacterium tuberculosis. A point mutation in either codon 516, 526, or 531 was found in 13 strains requiring MICs of > or = 64 micrograms/ml, while 21 strains requiring MICs of < or = 1 microgram/ml showed no alteration in these codons. However, 3 of these 21 strains contained a point mutation in either codon 515 or 533. Of the other six strains requiring MICs between 2 and 32 micrograms/ml, three contained a point mutation in codon 516 or 526, while no alteration was detected in the other three. Our results indicate that the sequencing analysis of a 69-bp fragment in the rpoB gene is useful in predicting rifampin-resistant phenotypes.

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.

scholarly journals Comparison of Mycobacterium tuberculosis Genomes Reveals Frequent Deletions in a 20 kb Variable Region in Clinical Isolates

Yeast ◽  
2000 ◽  
Vol 1 (4) ◽  
pp. 272-282
Author(s):  
Timothy B. L. Ho ◽  
Brian D. Robertson ◽  
G. Michael Taylor ◽  
Rory J. Shaw ◽  
Douglas B. Young
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hot Spots ◽  
High Frequency ◽  
Biological Diversity ◽  
Variable Region ◽  
Clinical Isolates ◽  
Insertion Element ◽  
Genomic Deletions ◽  
Nucleotide Repeats ◽  
Strain H37rv

The Mycobacterium tuberculosis complex is associated with a remarkably low level of structural gene polymorphism. As part of a search for alternative forms of genetic variation that may act as a source of biological diversity in M. tuberculosis, we have identified a region of the genome that is highly variable amongst a panel of unrelated clinical isolates. Fifteen of 24 isolates examined contained one or more copies of the M. tuberculosis-specific IS6110 insertion element within this 20 kb variable region. In nine of the isolates, including the laboratory-passaged strain H37Rv, genomic deletions were identified, resulting in loss of between two and 13 genes. In each case, deletions were associated with the presence of a copy of the IS6110 element. Absence of flanking tri- or tetra-nucleotide repeats identified homologous recombination between adjacent IS6110 elements as the most likely mechanism of the deletion events. IS6110 insertion into hot-spots within the genome of M. tuberculosis provides a mechanism for generation of genetic diversity involving a high frequency of insertions and deletions.

Rifampin-resistance-associated mutations in the rifampin-resistance-determining region of the rpoB gene of Mycobacterium tuberculosis clinical isolates in Shanghai, PR China

2021 ◽  
Author(s):  
Yinjuan Guo ◽  
Xingwei Cao ◽  
Jinghui Yang ◽  
Xiaocui Wu ◽  
Yin Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type Species ◽  
Mutation Frequency ◽  
Rpob Gene ◽  
Clinical Isolates ◽  
Content Type ◽  
Link Type ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Rifampin Resistance

Introduction. Resistance to rifampin (RIF) in Mycobacterium tuberculosis infection is associated with mutations in the rpoB gene coding for the β-subunit of RNA polymerase. The contribution of various rpoB mutations to the development and level of RIF resistance remains elusive. Hypothesis/Gap Statement. Various rpoB mutations may be associated with differential levels of RIF resistance. Aim. This study aimed to investigate the relationship between specific rpoB mutations and the MICs of RIF and rifabutin (RFB) against M. tuberculosis . Methodology. Of the 195 clinical isolates, 105 and 90 isolates were randomly selected from isolates resistant to RIF and sensitive to RIF, respectively. The MICs of 12 agents for M. tuberculosis isolates were determined using commercial Sensititre M. tuberculosis MIC plates and the broth microdilution method. Strains were screened for rpoB mutations by DNA extraction, rpoB gene amplification and DNA sequence analysis. Results. One hundred isolates (95.24 %) were found to have mutations in the RIF-resistance-determining region (RRDR) of the rpoB gene. Three rpoB mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90 %) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codons 450 and 445. We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the rpoB gene in two strains (1.90 %) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 450 was significantly higher in RIF-resistant/RFB-resistant (RIFR/RFBR) strains than in RIFR/RFBS strains (75.58 % versus 21.05 %, P<0.01), whereas the mutation frequency at codon 435 was significantly lower in RIFR/RFBR strains than in RIFR/RFBS strains (1.16 % versus 26.32 %, P<0.01). Conclusion. Our data support previous findings, which reported that various rpoB mutations are associated with differential levels of RIF resistance. The specific mutations in the rpoB gene in RIFR/RFBR isolates differed from those in the RIFR/RFBS isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of infections caused by M. tuberculosis strains harbouring these mutations.

Rifampin resistance-associated mutations in the RIF resistance-determining region (RRDR) of the rpoB gene of Mycobacterium tuberculosis clinical isolates in Shanghai, China

2019 ◽  
Author(s):  
Yinjuan Guo ◽  
Xingwei Cao ◽  
Jinghui Yang ◽  
Xiaocui Wu ◽  
Yin Liu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mutation Frequency ◽  
Rpob Gene ◽  
Clinical Isolates ◽  
Sequencing Analysis ◽  
Mycobacterium Tuberculosis Infection ◽  
Gene Coding ◽  
Rifampin Resistance ◽  
Dna Sequencing Analysis ◽  
The Relationship

Abstract Background: Resistance to rifampin (RIF) in Mycobacterium tuberculosis infection is associated with mutations in the rpoB gene coding for the beta-subunit of RNA polymerase. The contribution of many individual rpoB mutations to the development and level of RIF resistance remains elusive. Our objective for this study was to investigate the relationship between specific rpoB mutations and the minimum inhibitory concentrations (MICs) of RIF and rifabutin (RFB) against M.tuberculosis. Methods: We collected 195 clinical isolates of M. tuberculosis including 105 RIF-resistant and 90 RIF-susceptible isolates from Shanghai Pulmonary Hospital in China. The MICs of antituberculosis drugs in 7H10 Middlebrook medium for clinical isolates of M. tuberculosis were determined. Strains were screened for rpoB mutations by DNA extraction, rpoB gene amplification, and DNA sequencing analysis. Results: Twenty different types of mutations were identified in the rpoB gene. One hundred isolates (95.24%) were found to have mutations in the RIF resistance-determining region (RRDR) of the rpoB gene. Three rpoB mutations were identified in 90 RIF-susceptible isolates. Out of 105 isolates, 86 (81.90%) were cross-resistant to both RIF and RFB. The most frequent mutation occurred at codon 531 (65.71%), followed by 526 (8.57%). We also found a novel nine-nucleotide (ATCATGCAT) deletion (between positions 1543 and 1551) in the rpoB gene among two strains (1.90%) with resistance to RIF, but susceptibility to RFB. In addition, the mutation frequency at codon 531 was significantly higher in RIF-resistant/RFB-resistant (RIFR/RFBR) strains than in RIFR/RFBS strains (75.58% versus 21.05%), whereas the mutation frequency at codon 516 was significantly lower in RIFR/RFBR strains than in RIFR/RFBS strains (1.16% versus 26.32%). The MICs of RIF against 87.62% (92/105) of the M.tuberculosis isolates were ≥ 16 µg/mL. Conclusions: Our data supported previous findings that various rpoB mutations are associated with differential levels of resistance to RIF. The specific mutations of the rpoB gene in RIFR/RFBR isolates differed from those in RIFR/RFBS isolates. A novel deletion mutation in the RRDR might be associated with resistance to RIF, but not to RFB. Further clinical studies are required to investigate the efficacy of RFB in the treatment of M. tuberculosis infections, which harbor the mutations.

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