Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates

The ahpC genes of 57 clinical isolates and one in vitro mutant of Mycobacterium tuberculosis were evaluated by nucleotide sequence analyses. Although compensatory ahpC promoter mutations were identified in 8 catalase-negative, katG-defective strains, the ahpC genes of 25 catalase-positive, isoniazid-resistant isolates and 25 drug-sensitive strains were not altered.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00303-06 ◽

2006 ◽

Vol 50 (8) ◽

pp. 2860-2862 ◽

Cited By ~ 31

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.

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Rapid detection of specific gene mutations associated with isoniazid or rifampicin resistance in Mycobacterium tuberculosis clinical isolates using non-fluorescent low-density DNA microarrays

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkl058 ◽

2006 ◽

Vol 57 (5) ◽

pp. 825-831 ◽

Cited By ~ 37

Author(s):

Lina Marcela Aragón ◽

Ferran Navarro ◽

Volker Heiser ◽

Montserrat Garrigó ◽

Montserrat Español ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Rapid Detection ◽

Dna Microarrays ◽

Gene Mutations ◽

Clinical Isolates ◽

Rifampicin Resistance ◽

Specific Gene ◽

Low Density

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Reevaluation of the Critical Concentration for Drug Susceptibility Testing of Mycobacterium tuberculosis against Pyrazinamide Using Wild-Type MIC Distributions andpncAGene Sequencing

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05894-11 ◽

2011 ◽

Vol 56 (3) ◽

pp. 1253-1257 ◽

Cited By ~ 35

Author(s):

J. Werngren ◽

E. Sturegård ◽

P. Juréen ◽

K. Ängeby ◽

S. Hoffner ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Critical Concentration ◽

Gene Mutations ◽

Drug Susceptibility ◽

Drug Susceptibility Testing ◽

Clinical Isolates ◽

Wild Type ◽

First Line ◽

Content Type ◽

Resistant Strains

ABSTRACTPyrazinamide (PZA) is a potent first-line agent for the treatment of tuberculosis (TB) with activity also against a significant part of drug-resistantMycobacterium tuberculosisstrains. Since PZA is active only at acid pH, testing for susceptibility to PZA is difficult and insufficiently reproducible. The recommended critical concentration for PZA susceptibility (MIC, 100 mg/liter) used in the Bactec systems (460 and MGIT 960) has not been critically evaluated against wild-type MIC distributions in clinical isolates ofMycobacterium tuberculosis. Using the Bactec MGIT 960 system, we determined the PZA MICs for 46 clinicalM. tuberculosisisolates and compared the results topncAsequencing and previously obtained Bactec 460 data. For consecutive clinical isolates (n= 15), the epidemiological wild-type cutoff (ECOFF) for PZA was 64 mg/liter (MIC distribution range, ≤8 to 64 mg/liter), and nopncAgene mutations were detected. In strains resistant in both Bactec systems (n= 18), the PZA MICs ranged from 256 to ≥1,024 mg/liter. The discordances betweenpncAsequencing, susceptibility results in Bactec 460, and MIC determinations in Bactec MGIT 960 were mainly observed in strains with MICs close to or at the ECOFF. We conclude that in general, wild-type and resistant strains were clearly separated and correlated topncAmutations, although some isolates with MICs close to the ECOFF cause reproducibility problems within and between methods. To solve this issue, we suggest that isolates with MICs of ≤64 mg/liter be classified susceptible, that an intermediary category be introduced at 128 mg/liter, and that strains with MICs of >128 mg/liter be classified resistant.

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Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates in Southern China

Infection and Drug Resistance ◽

10.2147/idr.s230774 ◽

2020 ◽

Vol Volume 13 ◽

pp. 217-227 ◽

Cited By ~ 1

Author(s):

HM Adnan Hameed ◽

Yaoju Tan ◽

Md Mahmudul Islam ◽

Zhili Lu ◽

Chiranjibi Chhotaray ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Southern China ◽

Gene Mutations ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Novel Gene

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Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China

Epidemiology and Infection ◽

10.1017/s0950268899003635 ◽

2000 ◽

Vol 124 (2) ◽

pp. 227-232 ◽

Cited By ~ 26

Author(s):

L. HOU ◽

D. OSEI-HYIAMAN ◽

Z. ZHANG ◽

B. WANG ◽

A. YANG ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Amino Acid ◽

Molecular Basis ◽

Gene Mutations ◽

Clinical Isolates ◽

Start Codon ◽

Nucleotide Position ◽

Nucleotide Substitutions ◽

Base Pair Deletion

A sample of 35 pyrazinamide (PZA)-resistant and 30 PZA-susceptible clinical isolates recovered from Beijing and Taiyuan City, China were characterized by SSCP and sequence analysis for mutations in the pncA gene that encodes the Mycobacterium tuberculosis PZase. The purpose of this study was to understand the molecular basis and the characteristics of pncA gene mutations and its relation to PZA resistance in M. tuberculosis strains from China. Several mutations with base changes leading to amino acid substitutions were found in the PZA-resistant isolates. No mutations were seen in the 243 PZA-susceptible isolates. Among the 35 PZA-resistant isolates, 32 isolates (91·4%) had nucleotide substitutions, insertions and deletions that resulted in amino-acid substitution; or frameshifts in some strains. Other previously uncharacterized mutations were found as follows: Asn118→Thr, CG insertion at position 501; CC insertion at nucleotide position 403; a 8 base-pair deletion at start codon; Pro54→Thr; AG insertion at 368; Tyr41→His, Ser88→stop, and A insertion at nucleotide position 301. IS6110 subtyping revealed that each strain was unique; indicative of the epidemiologic independence of the isolates.

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