scholarly journals Investigation of Ser315 Substitutions withinkatGGene in Isoniazid-Resistant Clinical Isolates ofMycobacterium tuberculosisfrom South India

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
A. Nusrath Unissa ◽  
N. Selvakumar ◽  
Sujatha Narayanan ◽  
C. Suganthi ◽  
L. E. Hanna
Keyword(s):  
Mycobacterium Tuberculosis ◽  
South India ◽  
Inhibitory Concentration ◽  
Direct Sequencing ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
Sequencing Method ◽  
High Prevalence ◽  
Direct Sequencing Method ◽  
High Level

Mutation at codon 315 ofkatGgene is the major cause for isoniazid (INH) resistance inMycobacterium tuberculosis(M. tuberculosis). Substitution at codon 315 ofkatGgene was analyzed in 85 phenotypically resistant isolates collected from various parts of southern India by direct sequencing method. The obtained results were interpreted in the context of minimum inhibitory concentration (MIC) of INH. Of the 85 phenotypically resistant isolates, 56 (66%) were also correlated by the presence of resistance mutations in thekatGgene; 47 of these isolates had ACC, 6 had AAC, 2 had ATC, and one had CGC codon. The frequency of Ser315 substitution inkatGgene was found to be higher (70%) amongst multidrug-resistant (MDR) strains than among non-MDR (61%) INH-resistant isolates. Further, the frequency of mutations was found to be greater (74%) in isolates with higher MIC values in contrast to those isolates with low MIC values (58%). Therefore, the study identified high prevalence of Ser315Thr substitution inkatGgene of INH-resistant isolates from south India. Also, isolates harboring this substitution were found to be associated with multidrug and high level INH resistance.

scholarly journals Mutations ingyrAandgyrBamong Fluoroquinolone- and Multidrug-Resistant Mycobacterium tuberculosis Isolates

2016 ◽  
Vol 60 (4) ◽  
pp. 2090-2096 ◽  
Author(s):  
Jung-Yien Chien ◽  
Wei-Yih Chiu ◽  
Shun-Tien Chien ◽  
Chia-Jung Chiang ◽  
Chong-Jen Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
East Asian ◽  
Multidrug Resistant ◽  
Molecular Techniques ◽  
Content Type ◽  
Low Level ◽  
High Prevalence ◽  
Mdr Tb ◽  
High Level

ABSTRACTIn order to correlate the mutations inside the entiregyrAandgyrBgenes with the level of resistance to ofloxacin (OFX) and moxifloxacin (MFX) in isolates of multidrug-resistantMycobacterium tuberculosis(MDR-TB), a total of 111 isolates were categorized into OFX-susceptible (MIC, ≤2 μg/ml) and low-level (MIC, 4 to 8 μg/ml) and high-level (MIC, ≥16 μg/ml) OFX-resistant isolates and MFX-susceptible (MIC, ≤0.5 μg/ml) and low-level (MIC, 1 to 2 μg/ml) and high-level (MIC, ≥4 μg/ml) MFX-resistant isolates. Resistance-associated mutations inside thegyrAgene were found in 30.2% of OFX-susceptible and 72.5% and 72.2% of low-level and high-level OFX-resistant isolates and in 28.6% of MFX-susceptible and 58.1% and 83.9% of low-level and high-level MFX-resistant isolates. Compared with OFX-susceptible isolates, low-level and high-level OFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (17.0%, 65.0%, and 72.2%, respectively;P< 0.001) and a higher prevalence of thegyrBG512R mutation (0.0%, 2.5%, and 16.7%, respectively;P= 0.006). Similarly, compared with MFX-susceptible isolates, low-level and high-level MFX-resistant isolates had a significantly higher prevalence of mutations atgyrAcodons 88 to 94 (14.3%, 51.6%, and 80.6%, respectively;P< 0.001) as well as a higher prevalence of thegyrBG512R mutation (0.0%, 0.0%, and 12.9%, respectively;P= 0.011). D94G and D94N mutations ingyrAand the G512R mutation ingyrBwere correlated with high-level MFX resistance, while the D94A mutation was associated with low-level MFX resistance. The prevalence of mutations atgyrAcodons 88 to 94 and thegyrBG512R mutation were higher among fluoroquinolone (FQ)-susceptible East Asian (Beijing) and Indo-Oceanic strains than they were among Euro-American strains, implying that molecular techniques to detect FQ resistance may be less specific in areas with a high prevalence of East Asian (Beijing) and Indo-Oceanic strains.

scholarly journals Clinical utility of the HCV drug resistance assay using the direct sequencing method and the cycleave PCR method in the dual therapy with daclatasvir and asunaprevir

Kanzo ◽  
2015 ◽  
Vol 56 (10) ◽  
pp. 533-535 ◽  
Author(s):  
Hideyuki Kudoh ◽  
Yoko Nagasawa ◽  
Michiru Ito ◽  
Nobuko Watanabe ◽  
Isao Naruse ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Utility ◽  
Direct Sequencing ◽  
Dual Therapy ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Pcr Method

scholarly journals Constraints of Drug Resistance in Mycobacterium tuberculosis - Prospects for Pharmacological Reversion of Susceptibility to Antibiotics

2017 ◽  
Vol 8 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Aleksandr I. Ilin ◽  
Murat E. Kulmanov ◽  
Ilya S. Korotetskiy ◽  
Marina V. Lankina ◽  
Gulshara K. Akhmetova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Genetic Heterogeneity ◽  
Multidrug Resistant ◽  
Resistance Mutations ◽  
General Increase ◽  
Drug Induced ◽  
Mdr Tb ◽  
Resistant Strains

Emergence of multidrug resistant strains ofMycobacterium tuberculosis(MDR-TB) threatens humanity. This problem was complicated by the crisis in development of new anti-tuberculosis antibiotics. Induced reversion of drug resistance seems promising to overcome the problem. Successful clinical trial of a new anti-tuberculosis nanomolecular complex FS-1 has demonstrated prospectively of this approach in combating MDR-TB. Several clinical MDR-TB cultures were isolated from sputum samples prior and in the process of the clinical trial. Every isolate was tested for susceptibility to antibiotics and then they were sequenced for comparative genomics. It was found that the treatment with FS-1 caused an increase in the number of antibiotic susceptible strains among Mtb isolates that was associated with a general increase of genetic heterogeneity of the isolates. Observed impairing of phthiocerol dimycocerosate biosynthesis by disruptive mutations inppsACDsubunits indicated a possible virulence remission for the sake of persistence. It was hypothesized that the FS-1 treatment eradicated the most drug resistant Mtb variants from the population by aggravating the fitness cost of drug resistance mutations. Analysis of distribution of these mutations in the global Mtb population revealed that many of them were incompatible with each other and dependent on allelic states of many other polymorphic loci. The latter discovery may explain the negative correlation between the genetic heterogeneity of the population and the level of drug tolerance. To the best of our knowledge, this work was the first experimental confirmation of the drug induced antibiotic resistance reversion by the induced synergy mechanism that previously was predicted theoretically.

scholarly journals Genome Sequencing of Polydrug-, Multidrug-, and Extensively Drug-Resistant Mycobacterium tuberculosis Strains from South India

2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Sivakumar Shanmugam ◽  
Narender Kumar ◽  
Dina Nair ◽  
Mohan Natrajan ◽  
Srikanth Prasad Tripathy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
South India ◽  
Sequence Data ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Extensively Drug Resistant

The genomes of 16 clinical Mycobacterium tuberculosis isolates were subjected to whole-genome sequencing to identify mutations related to resistance to one or more anti-Mycobacterium drugs. The sequence data will help in understanding the genomic characteristics of M. tuberculosis isolates and their resistance mutations prevalent in South India.

scholarly journals A Functional Polymorphism in the Promoter Region of Interleukin-12B Increases the Risk of Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yabin Liu ◽  
Binghui Li ◽  
Lili Wang ◽  
Dexian Kong
Keyword(s):  
Colorectal Cancer ◽  
Direct Sequencing ◽  
Transcriptional Level ◽  
Mrna Levels ◽  
Normal Tissues ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Healthy Control ◽  
Polymerase Chain ◽  
Interleukin 12B

Objective. To investigate whether the polymorphisms of interleukin-12B (IL-12B) were associated with the risk of developing colorectal cancer (CRC). Patients and Methods. Genotypes of rs17860508 and rs3212227 were determined by polymerase chain reaction with a direct sequencing method in 329 CRC patients and 342 matched healthy control subjects. The expression of IL-12B mRNA was determined by RT-qPCR in 50 pairs of CRC tissues and their adjacent normal tissues. Results. Compared with TTAGAG/TTAGAG genotype of rs17860508, the GC/GC and TTAGAG/GC genotypes may significantly increase the risk of CRC (OR = 1.81, 95% CI = 1.18–2.78; OR = 1.46, 95% CI = 1.01–2.12, respectively). Furthermore, the mRNA levels of IL-12B were significantly higher in the CRC tissues from patients with the rs17860508 GC/GC genotype than those with the TTAGAG/GC (P=0.009) and TTAGAG/TTAGAG (P=0.001) genotypes. Conclusion. These data suggested that the rs17860508 GC/GC genotype might upregulate IL-12B expression at the transcriptional level and thus increase the risk of CRC.

scholarly journals Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Jiang Rong ◽  
Ma Chunhua ◽  
Lv Yuan ◽  
Mu Ning ◽  
Li Jinduo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lung Adenocarcinoma ◽  
Gene Mutation ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Egfr Mutations ◽  
Egfr Gene ◽  
Sequencing Method ◽  
Direct Sequencing Method ◽  
Egfr Gene Mutation

AbstractObjectiveTo discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.Methods5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid.Results5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method.ConclusionARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

scholarly journals Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates

2015 ◽  
Vol 59 (12) ◽  
pp. 7805-7810 ◽  
Author(s):  
Johana Rueda ◽  
Teresa Realpe ◽  
Gloria Isabel Mejia ◽  
Elsa Zapata ◽  
Juan Carlos Rozo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Content Type ◽  
Genotypic Analysis ◽  
Mdr Tb ◽  
Proportion Method ◽  
Emergence Of Resistance ◽  
Phenotypic Susceptibility

ABSTRACTEthionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in theMycobacterium tuberculosispopulation. ETH resistance inM. tuberculosisis phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in theinhApromoter and in the following genes:katG,ethA,ethR,mshA,ndh, andinhA. We sequenced the above genes in 64M. tuberculosisisolates (n= 57 ETH-resistant MDR-TB isolates;n= 3 ETH-susceptible MDR-TB isolates; andn= 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% inkatG, 72% inethA, 45.6% inmshA, 8.7% inndh, and 33.3% ininhAor its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations inkatG; one had a mutation inethA, and another, inmshAandinhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations inmshAgene unrelated to the resistance. Mutations not previously reported were found in theethA,mshA,katG, andndhgenes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in theM. tuberculosisisolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

scholarly journals Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Rong-hua Song ◽  
Qian Li ◽  
Wen Wang ◽  
Qiu-ming Yao ◽  
Xiao-qing Shao ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Thyroid Disease ◽  
Gene Polymorphisms ◽  
Autoimmune Thyroid Disease ◽  
Direct Sequencing ◽  
Autoimmune Thyroid ◽  
Interleukin 22 ◽  
Sequencing Method ◽  
Thyroid Associated Ophthalmopathy ◽  
Direct Sequencing Method

As there are no previous studies on the interleukin-22 (IL-22) variants in autoimmune thyroid disease (AITD), the present study aimed to explore the association between polymorphisms of IL-22 and the predisposition to AITD. The study had 975 AITD patients, including 639 Graves’ disease (GD) and 336 Hashimoto’s thyroiditis (HT) individuals and 851 healthy cohorts. Ligase detection reaction (LDR) and direct sequencing method were used for genotyping the IL-22 gene polymorphisms at rs2046068, rs2227478, rs2227485, rs11611206, and rs1179251. In comparison to female controls, genotype CC of rs1179251 was increased in the female AITD patients. Alleles C at rs2046068, C at rs2227478, and C at rs1179251 linked to the susceptibility of HT males. Genotype CC in rs1179251 was higher in male HT. Variants at rs2046068, rs2227478, and rs1179251 were associated with the AITD teenagers. Besides, genotype GG in rs11611206 was correlated with thyroid-associated ophthalmopathy (TAO). Moreover, allele G at rs11611206 was associated with decreased risk for TAO by 28.9%. Similarly, genotype CC of rs1179251 and genotype GG of rs11611206 were associated with Graves’ ophthalmopathy (GO). Allele G in rs11611206 increased people with HT towards the predisposition of hypothyroidism. In conclusion, genetic variants of IL-22 are associated with the occurrence of AITD.

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