scholarly journals Novel mutation in 16S rRNA associated with streptomycin dependence in Mycobacterium tuberculosis

1995 ◽  
Vol 39 (3) ◽  
pp. 769-770 ◽  
Author(s):  
N. Honore ◽  
G. Marchal ◽  
S. T. Cole
Keyword(s):  
Mycobacterium Tuberculosis ◽  
16S Rrna ◽  
Novel Mutation

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Quantitative Analysis of mRNA as a Marker for Viability of Mycobacterium tuberculosis

1999 ◽  
Vol 37 (2) ◽  
pp. 290-295 ◽  
Author(s):  
T. J. Hellyer ◽  
L. E. DesJardin ◽  
G. L. Hehman ◽  
M. D. Cave ◽  
K. D. Eisenach
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Quantitative Analysis ◽  
16S Rrna ◽  
Therapeutic Efficacy ◽  
Rapid Determination ◽  
Drug Susceptibility ◽  
Resistant Strains ◽  
Time Required ◽  
Rrna Sequences

Numerous assays which use conserved DNA or rRNA sequences as targets for amplification have been described for the diagnosis of tuberculosis. However, these techniques have not been applied successfully to the monitoring of therapeutic efficacy owing to the persistence of amplifiable nucleic acid beyond the point at which smears and cultures become negative. Semiquantitative analysis of rRNA has been used to reduce the time required for antimicrobial susceptibility testing of Mycobacterium tuberculosis, although growth for up to 5 days in the presence of some drugs is still required to discriminate resistant strains. The purpose of the present study was to determine whether quantitative analysis of M. tuberculosis mRNA could be used to assess bacterial viability and to illustrate the application of this technique to rapid determination of drug susceptibility. Levels of mRNA encoding the 85B protein (α-antigen), IS6110 DNA, and 16S rRNA were compared in parallel cultures of M. tuberculosis that were treated with either no drug, 0.2 μg of isoniazid per ml, or 1 μg of rifampin per ml. Exposure of sensitive strains to isoniazid or rifampin for 24 h reduced the levels of 85B mRNA to <4 and <0.01%, respectively, of those present in control cultures without drug. In contrast, the levels of IS6110 DNA and 16S rRNA did not diminish over the same period. Strains which were resistant to either isoniazid or rifampin demonstrated no reduction in 85B mRNA in the presence of the drug to which they were nonresponsive. Quantitative analysis of 85B mRNA offers a potentially useful tool for the rapid determination of M. tuberculosis drug susceptibility and for the monitoring of therapeutic efficacy.

scholarly journals Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

2018 ◽  
Author(s):  
Yousif Mohammed Alfatih ◽  
Abeer Babiker Idris ◽  
Hadeel Gassim Hassan ◽  
Eman O M Nour ◽  
Nihad M A Elhaj ◽  
...  
Keyword(s):  
16S Rrna ◽  
Molecular Mechanisms ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
World Health ◽  
Bacterial Disease ◽  
Global Public Health ◽  
Mdr Tb ◽  
Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

scholarly journals RFLP clusters of rifampicin resistant and susceptible Mycobacterium tuberculosis strains in Western province of Sri Lanka

2017 ◽  
Vol 11 (08) ◽  
pp. 619-625
Author(s):  
Chamila Priyangani Adikaram ◽  
Sandya Sulochana Wijesundera ◽  
Jennifer Perera
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Sri Lanka ◽  
Novel Mutation ◽  
Point Mutations ◽  
Clonal Expansion ◽  
Rpob Gene ◽  
The Novel ◽  
Western Province ◽  
Control And Prevention

Introduction: Continuous studies on genetic diversity of Mycobacterium tuberculosis could enhance the awareness on transmission, control and prevention of tuberculosis (TB). In this study, we investigated current genetic diversity of TB and rifampicin resistant TB by, Restriction Fragment Length Polymorphism (RFLP) based on fingerprinting of the IS6110 insertion sequence, in the Western province of Sri Lanka, the famous touristic destination with the highest TB burden in the country. Methodology: Genomic DNA extracted from susceptible and rifampicin resistant TB strains (confirmed for rpoB gene point mutations) were digested with PvuII restriction enzyme, electrophoresed and subjected to Southern transfer. The blots were hybridised with IS6110 probe and visualized using a chemiluminescence detection. Results: The number of copies of IS6110 per isolate varied from 1 to 14. The dendrogram revealed a total of 68 distinct strains among 77 TB isolates and they belonged to nine clusters. Both rifampicin resistant and susceptible strains were distributed in all clusters. This evaluation revealed the absence of genetically identical or strong relatedness between susceptible and resistant isolates. However, clonal expansion was detected in transmission of both TB and rifampicin resistant TB. In addition, the resistant isolates having the novel mutation had no clonal relatedness. Conclusion: This is the first observational study regarding clonal expansion of TB in Sri Lanka. Thus, further investigation on genotypes, clonal expansion and transmission of drug resistance using additional markers would be useful for controlling TB.

scholarly journals A Mutation in the 16S rRNA Decoding Region Attenuates the Virulence of Mycobacterium tuberculosis

2016 ◽  
Vol 84 (8) ◽  
pp. 2264-2273 ◽  
Author(s):  
Shinya Watanabe ◽  
Kazunori Matsumura ◽  
Hiroki Iwai ◽  
Keiji Funatogawa ◽  
Yuji Haishima ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
16S Rrna ◽  
Binding Sites ◽  
Mycolic Acid ◽  
Acid Biosynthesis ◽  
Mutation Site ◽  
Content Type ◽  
Antigen 85 ◽  
Decoding Region

Mycobacterium tuberculosiscontains a single rRNA operon that encodes targets for antituberculosis agents, including kanamycin. To date, only four mutations in the kanamycin binding sites of 16S rRNA have been reported in kanamycin-resistant clinical isolates. We hypothesized that another mutation(s) in the region may dramatically decreaseM. tuberculosisviability and virulence. Here, we describe an rRNA mutation, U1406A, which was generatedin vitroand confers resistance to kanamycin while highly attenuatingM. tuberculosisvirulence. The mutant showed decreased expression of 20% (n= 361) of mycobacterial proteins, including central metabolic enzymes, mycolic acid biosynthesis enzymes, and virulence factors such as antigen 85 complexes and ESAT-6. The mutation also induced three proteins, including KsgA (Rv1010; 16S rRNA adenine dimethyltransferase), which closely bind to the U1406A mutation site on the ribosome; these proteins were associated with ribosome maturation and translation initiation processes. The mutant showed an increase in 17S rRNA (precursor 16S rRNA) and a decrease in the ratio of 30S subunits to the 70S ribosomes, suggesting that the U1406A mutation in 16S rRNA attenuatedM. tuberculosisvirulence by affecting these processes.

scholarly journals Molecular Characterization of Isoniazid Resistance in Mycobacterium tuberculosis: Identification of a Novel Mutation in inhA

2006 ◽  
Vol 50 (3) ◽  
pp. 1075-1078 ◽  
Author(s):  
E. T. Y. Leung ◽  
P. L. Ho ◽  
K. Y. Yuen ◽  
W. L. Woo ◽  
T. H. Lam ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Characterization ◽  
Clinical Isolate ◽  
South China ◽  
Novel Mutation ◽  
Strong Association ◽  
Isoniazid Resistance ◽  
Allele Specific ◽  
China Region

ABSTRACT Multiplex allele-specific PCRs detecting katG codon 315 and mabA (bp −15) mutations could specifically identify 77.5% of isoniazid-resistant Mycobacterium tuberculosis strains in the South China region. One clinical isolate harboring InhA Ile194Thr was characterized to show strong association with isoniazid resistance in Mycobacterium tuberculosis.

Nanodiagnostic Method for Colorimetric Detection of Mycobacterium tuberculosis 16S rRNA

2008 ◽  
Vol 4 (1-4) ◽  
pp. 28-35 ◽  
Author(s):  
Pooria Gill ◽  
Mostafa Ghalami ◽  
Amir Ghaemi ◽  
Nader Mosavari ◽  
Hossein Abdul-Tehrani ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
16S Rrna ◽  
Colorimetric Detection
Sign in / Sign up

Export Citation Format

Share Document