scholarly journals Mechanism of Resistance to Amikacin and Kanamycin in Mycobacterium tuberculosis

1998 ◽  
Vol 42 (5) ◽  
pp. 1295-1297 ◽  
Author(s):  
George J. Alangaden ◽  
Barry N. Kreiswirth ◽  
Arlette Aouad ◽  
Minoo Khetarpal ◽  
Felicitas R. Igno ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Single Copy ◽  
Kanamycin Resistance ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Strain Atcc ◽  
Mechanism Of Resistance ◽  
High Level

ABSTRACT An A1400G mutation of the rrs gene was identified inMycobacterium tuberculosis (MTB) strain ATCC 35827 and in 13 MTB clinical isolates resistant to amikacin-kanamycin (MICs, >128 μg/ml). High-level cross-resistance may result from such a mutation since MTB has a single copy of the rrs gene. Another mechanism(s) may account for high-level amikacin-kanamycin resistance in two mutants and lower levels of resistance in four clinical isolates, all lacking the A1400G mutation.

scholarly journals Multiplex PCR Amplimer Conformation Analysis for Rapid Detection of gyrA Mutations in Fluoroquinolone-Resistant Mycobacterium tuberculosis Clinical Isolates

2004 ◽  
Vol 48 (2) ◽  
pp. 596-601 ◽  
Author(s):  
Augustine F. B. Cheng ◽  
Wing W. Yew ◽  
Edward W. C. Chan ◽  
Miu L. Chin ◽  
Mamie M. M. Hui ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multiplex Pcr ◽  
Region Of Interest ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Nucleotide Sequencing ◽  
Phenotypic Resistance ◽  
New Strategy ◽  
High Level

ABSTRACT A new strategy known as multiplex PCR amplimer conformation was developed for detection of mutation in the gyrA gene of 138 clinical isolates of Mycobacterium tuberculosis. The method generated a single-stranded and heteroduplex DNA banding pattern of multiplex PCR amplimers of the region of interest that was extremely sensitive to specific mutations, thus enabling much more sensitive and reliable mutation analysis compared to the standard single-stranded conformation polymorphism technique. The genetic profiles of the gyrA gene of the 138 isolates as detected by MPAC were confirmed by nucleotide sequencing and were found to correlate strongly with the in vitro susceptibilities of the mutant strains to six fluoroquinolones (ofloxacin, levofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, and sitafloxacin). All 32 isolates that contained gyrA mutations exhibited cross-resistance to the six fluoroquinolones (ofloxacin MIC for 90% of strains > 16 mg/liter), although moxifloxacin, gatifloxacin, and sitafloxacin (MIC for 90% of strains ≤ 4 mg/liter) were apparently more active than ofloxacin, levofloxacin, and sparfloxacin (MIC for 90% of strains ≥ 16 mg/liter). All gyrA mutations were clustered in codons 90, 91, and 94, and aspartic acid 94 was most frequently mutated. Twenty-three isolates without gyrA mutations were also found to exhibit reduced susceptibility to ofloxacin (MIC for 90% of strains = 4 mg/liter), but largely remained susceptible to other drugs (MIC for 90% of strains ≤ 1 mg/liter). Another 83 isolates without mutations were fully susceptible to all six fluoroquinolones (ofloxacin MIC for 90% of strains = 1 mg/liter). In conclusion, high-level phenotypic resistance to fluoroquinolones among M. tuberculosis clinical isolates, which appears to be predominantly due to gyrA mutations, may be readily detected by genotyping techniques such as multiplex PCR amplimer conformation.

Association of ubiA mutations and high-level of ethambutol resistance among Mycobacterium tuberculosis Thai clinical isolates

Tuberculosis ◽  
2019 ◽  
Vol 114 ◽  
pp. 42-46 ◽  
Author(s):  
Orawan Tulyaprawat ◽  
Angkana Chaiprasert ◽  
Piriyaporn Chongtrakool ◽  
Kamol Suwannakarn ◽  
Popchai Ngamskulrungroj
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clinical Isolates ◽  
High Level

scholarly journals Metronidazole Resistance in Prevotella spp. and Description of a New nim Gene in Prevotella baroniae

2009 ◽  
Vol 54 (1) ◽  
pp. 60-64 ◽  
Author(s):  
C. Alauzet ◽  
F. Mory ◽  
C. Teyssier ◽  
H. Hallage ◽  
J. P. Carlier ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Prolonged Exposure ◽  
Tertiary Care ◽  
Single Copy ◽  
Clinical Isolates ◽  
Teaching Hospitals ◽  
Rrna Gene ◽  
Prolonged Incubation ◽  
Sequence Elements ◽  
High Level

ABSTRACT Nonduplicate clinical isolates of Prevotella spp. recovered from patients hospitalized between 2003 and 2006 in two French tertiary-care teaching hospitals were investigated for their susceptibility to metronidazole and the presence of nim genes. Of the 188 strains tested, 3 isolates displayed reduced susceptibility to metronidazole after 48 h of incubation, while 27 additional isolates exhibited heterogeneous resistance after prolonged incubation; all 30 of the isolates were nim negative. Among the remaining 158 isolates, 7 nim-positive isolates were detected. All of these strains were identified as Prevotella baroniae by 16S rRNA gene sequence analysis and contained a new nim gene, named nimI, as determined by DNA sequence analysis. Chromosomal localization of this single-copy gene was demonstrated in all clinical isolates as well as in type strain P. baroniae DSM 16972 by using Southern hybridization. No known associated insertion sequence elements were detected upstream of the nimI gene in any of the nim-positive strains by PCR mapping. After prolonged exposure to metronidazole, stable resistant subpopulations could be selected in nimI-positive Prevotella isolates (n = 6) as well as in nim-negative Prevotella isolates (n = 6), irrespective of their initial susceptibility to this antibiotic. This study is the first description of a new nitroimidazole resistance gene in P. baroniae which seems to be silent and which might be intrinsic in this species. Moreover, our findings highlight the fact that high-level resistance to metronidazole may be easily induced in both nim-positive and nim-negative Prevotella sp. strains.

scholarly journals Comparative study of enzymatic activities of new KatG mutants from low- and high-level isoniazid-resistant clinical isolates of Mycobacterium tuberculosis

Tuberculosis ◽  
2016 ◽  
Vol 100 ◽  
pp. 15-24 ◽  
Author(s):  
Florence Brossier ◽  
Marlène Boudinet ◽  
Vincent Jarlier ◽  
Stéphanie Petrella ◽  
Wladimir Sougakoff
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Comparative Study ◽  
Enzymatic Activities ◽  
Clinical Isolates ◽  
High Level

scholarly journals Disparities in Capreomycin Resistance Levels Associated with therrsA1401G Mutation in Clinical Isolates of Mycobacterium tuberculosis

2014 ◽  
Vol 59 (1) ◽  
pp. 444-449 ◽  
Author(s):  
Analise Z. Reeves ◽  
Patricia J. Campbell ◽  
Melisa J. Willby ◽  
James E. Posey
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Strong Predictor ◽  
Critical Concentration ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Second Line ◽  
Content Type

ABSTRACTAs the prevalence of multidrug-resistant and extensively drug-resistant tuberculosis strains continues to rise, so does the need to develop accurate and rapid molecular tests to complement time-consuming growth-based drug susceptibility testing. Performance of molecular methods relies on the association of specific mutations with phenotypic drug resistance and while considerable progress has been made for resistance detection of first-line antituberculosis drugs, rapid detection of resistance for second-line drugs lags behind. TherrsA1401G allele is considered a strong predictor of cross-resistance between the three second-line injectable drugs, capreomycin (CAP), kanamycin, and amikacin. However, discordance is often observed between therrsA1401G mutation and CAP resistance, with up to 40% ofrrsA1401G mutants being classified as CAP susceptible. We measured the MICs to CAP in 53 clinical isolates harboring therrsA1401G mutation and found that the CAP MICs ranged from 8 μg/ml to 40 μg/ml. These results were drastically different from engineered A1401G mutants generated in isogenicMycobacterium tuberculosis, which exclusively exhibited high-level CAP MICs of 40 μg/ml. These data support the results of prior studies, which suggest that the critical concentration of CAP (10 μg/ml) used to determine resistance by indirect agar proportion may be too high to detect all CAP-resistant strains and suggest that a larger percentage of resistant isolates could be identified by lowering the critical concentration. These data also suggest that differences in resistance levels among clinical isolates are possibly due to second site or compensatory mutations located elsewhere in the genome.

scholarly journals In VitroActivity of AZD5847 against Geographically Diverse Clinical Isolates of Mycobacterium tuberculosis

2014 ◽  
Vol 58 (7) ◽  
pp. 4222-4223 ◽  
Author(s):  
Jim Werngren ◽  
Maria Wijkander ◽  
Nasrin Perskvist ◽  
V. Balasubramanian ◽  
Vasan K. Sambandamurthy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lavage Fluid ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Cross Resistance ◽  
Drug Candidate ◽  
Content Type ◽  
Geographical Regions ◽  
Lung Biopsies

ABSTRACTThe MIC of the novel antituberculosis (anti-TB) drug AZD5847 was determined against 146 clinical isolates from diverse geographical regions, including eastern Europe, North America, Africa, and Asia, using the automated Bactec Mycobacterial Growth Indicator Tube (MGIT) 960 system. These isolates originated from specimen sources such as sputum, bronchial alveolar lavage fluid, pleural fluid, abscess material, lung biopsies, and feces. The overall MIC90was 1.0 mg/liter (range, 0.125 to 4 mg/liter). The MICs of AZD5847 for isolates ofMycobacterium tuberculosiswere similar among drug-sensitive strains, multidrug-resistant (MDR) strains, and extensively drug resistant (XDR) strains. The goodin vitroactivity of AZD5847 againstM. tuberculosisand the lack of cross-resistance make this agent a promising anti-TB drug candidate.

scholarly journals First Linezolid-Resistant Clinical Isolates of Mycobacterium tuberculosis

2007 ◽  
Vol 51 (4) ◽  
pp. 1534-1536 ◽  
Author(s):  
Elvira Richter ◽  
Sabine Rüsch-Gerdes ◽  
Doris Hillemann
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Mechanism Of Resistance ◽  
Potential Target ◽  
Linezolid Resistance

ABSTRACT Linezolid resistance was found in 4 (1.9%) of 210 multidrug-resistant Mycobacterium tuberculosis strains. The MICs of linezolid were 4 μg/ml (one strain) and 8 μg/ml (three strains). Since no mutations were detected in potential target genes, the mechanism of resistance remains unclear.

scholarly journals Contribution of rpoB Mutations to Development of Rifamycin Cross-Resistance in Mycobacterium tuberculosis

1998 ◽  
Vol 42 (7) ◽  
pp. 1853-1857 ◽  
Author(s):  
D. L. Williams ◽  
L. Spring ◽  
L. Collins ◽  
L. P. Miller ◽  
L. B. Heifets ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cross Resistance ◽  
In Vitro Mutagenesis ◽  
Missense Mutations ◽  
Resistance Mutations ◽  
Development Of Resistance ◽  
High Level ◽  
The Impact ◽  
Level Resistance

ABSTRACT The contributions of 23 insertion, deletion, or missense mutations within an 81-bp fragment of rpoB, the gene encoding the β-subunit of the DNA-dependent RNA polymerase of Mycobacterium tuberculosis, to the development of resistance to rifamycins (rifampin, rifabutin, rifapentine, and KRM-1648) in 29 rifampin-resistant clinical isolates were defined. Specific mutantrpoB alleles led to the development of cross-resistance to all rifamycins tested, while a subset of mutations were associated with resistance to rifampin and rifapentine but not to KRM-1648 or rifabutin. To further study the impact of specific rpoBmutant alleles on the development of rifamycin resistance, mutations were incorporated into the rpoB gene of M. tuberculosis H37Rv, contained on a mycobacterial shuttle plasmid, by in vitro mutagenesis. Recombinant M. tuberculosis clones containing plasmids with specific mutations in either codon 531 or 526 of rpoB exhibited high-level resistance to all rifamycins tested, whereas clones containing a plasmid with a mutation in codon 516 exhibited high-level resistance to rifampin and rifapentine but were susceptible to both rifabutin and KRM-1648. These results provided additional proof of the association of specificrpoB mutations with the development of rifamycin resistance and corroborate previous reports of the usefulness of rpoB genotyping for predicting rifamycin-resistant phenotypes.

Sign in / Sign up

Export Citation Format

Share Document