scholarly journals Examining the role of protein structural dynamics in drug resistance in Mycobacterium tuberculosis

2017 ◽  
Vol 8 (12) ◽  
pp. 8384-8399 ◽  
Author(s):  
Daniel J. Shaw ◽  
Rachel E. Hill ◽  
Niall Simpson ◽  
Fouad S. Husseini ◽  
Kirsty Robb ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Antimicrobial Resistance ◽  
Ir Spectroscopy ◽  
Structural Dynamics ◽  
2D Ir ◽  
Protein Structural Dynamics

2D-IR spectroscopy reveals a role for protein structural dynamics in antimicrobial-resistance.

scholarly journals Vibrational dynamics and solvatochromism of the label SCN in various solvents and hemoglobin by time dependent IR and 2D-IR spectroscopy

2014 ◽  
Vol 16 (36) ◽  
pp. 19643-19653 ◽  
Author(s):  
Luuk J. G. W. van Wilderen ◽  
Daniela Kern-Michler ◽  
Henrike M. Müller-Werkmeister ◽  
Jens Bredenbeck
Keyword(s):  
Hydrogen Bonding ◽  
Ir Spectroscopy ◽  
Structural Dynamics ◽  
Spectral Diffusion ◽  
Time Dependent ◽  
Vibrational Dynamics ◽  
2D Ir

The vibrational label SCN is used to report on local structural dynamics in a protein revealing spectral diffusion on a picosecond scale. The SCN spectra are compared to the response of methylthiocyanate in solvents with different polarity and hydrogen-bonding capabilities.

scholarly journals Role of embB Codon 306 Mutations in Mycobacterium tuberculosis Revisited: a Novel Association with Broad Drug Resistance and IS6110 Clustering Rather than Ethambutol Resistance

2005 ◽  
Vol 49 (9) ◽  
pp. 3794-3802 ◽  
Author(s):  
Manzour Hernando Hazbón ◽  
Miriam Bobadilla del Valle ◽  
Marta Inírida Guerrero ◽  
Mandira Varma-Basil ◽  
Ingrid Filliol ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Odds Ratio ◽  
Univariate Analysis ◽  
Drug Susceptibility ◽  
Drug Resistant ◽  
Development Of Resistance ◽  
Resistance Patterns ◽  
Novel Association

ABSTRACT Mutations at position 306 of embB (embB306) have been proposed as a marker for ethambutol resistance in Mycobacterium tuberculosis; however, recent reports of embB306 mutations in ethambutol-susceptible isolates caused us to question the biological role of this mutation. We tested 1,020 clinical M. tuberculosis isolates with different drug susceptibility patterns and of different geographical origins for associations between embB306 mutations, drug resistance patterns, and major genetic group. One hundred isolates (10%) contained a mutation in embB306; however, only 55 of these mutants were ethambutol resistant. Mutations in embB306 could not be uniquely associated with any particular type of drug resistance and were found in all three major genetic groups. A striking association was observed between these mutations and resistance to any drug (P < 0.001), and the association between embB306 mutations and resistance to increasing numbers of drugs was highly significant (P < 0.001 for trend). We examined the association between embB306 mutations and IS6110 clustering (as a proxy for transmission) among all drug-resistant isolates. Mutations in embB306 were significantly associated with clustering by univariate analysis (odds ratio, 2.44; P = 0.004). In a multivariate model that also included mutations in katG315, katG463, gyrA95, and kasA269, only mutations in embB306 (odds ratio, 2.14; P = 0.008) and katG315 (odds ratio, 1.99; P = 0.015) were found to be independently associated with clustering. In conclusion, embB306 mutations do not cause classical ethambutol resistance but may predispose M. tuberculosis isolates to the development of resistance to increasing numbers of antibiotics and may increase the ability of drug-resistant isolates to be transmitted between subjects.

scholarly journals Evaluation the Expression of Efflux Pump Genes “Tap & P55 in Mycobacterium Tuberculosis Clinical Isolates in Fars, Iran

2020 ◽  
Author(s):  
Fardis Khoob ◽  
Milad Shahini Shams Abadi ◽  
Nahal Hadi ◽  
Farzaneh Avazzadeh ◽  
Zahra Zarei
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Target Genes ◽  
Efflux Pump ◽  
Expression Level ◽  
Genetic Mutations ◽  
Antimicrobial Sensitivity ◽  
Probable Role ◽  
Tuberculosis Therapy

Abstract BackgroundThe increasing drug resistance in Mycobacterium tuberculosis isolates has become a global problem for tuberculosis therapy programs. Genetic mutations in rifampin (RIF), one of the key drugs in the treatment of tuberculosis are main mechanism of resistant to this drug in M. tuberculosis. Absence of mutation in target genes, other mechanisms such as efflux pump suggests possible role of drug resistant.The objective of this study was to find out mutations in rpoB genes in rifampin resistant isolates and to compare the expression level of tap and p55 efflux pump genes in non mutated isolates, mutated isolates in rpoB genes and susceptible isolates.MethodsIn this study, antimicrobial sensitivity test on first line drugs was performed on 200 M. tuberculosis isolates, obtained from TB center in Shiraz (IRAN) and genetic mutations were evaluated in rpoB gene in RIF resistant isolates by multiplex PCR, followed expression level evaluated by Real-time PCR.Resultsout of the 200 isolates tested, 23 (34.33%) showed resistant to RIF. 12 of 23 RIF resistant isolates have mutation in rpoB gene, and frequency of mutations in codons 516, 526 and 531 were 3 (25%), 4 (33.33%) and 5 (41.67%) respectively. The expression level of tap and p55 genes was considerably higher in resistant isolates which had no mutation compared to the expression level of genes in the isolates which had mutation in target genes.ConclusionThe accumulating data suggest the probable role of efflux pump in M. tuberculosis drug resistance, the validation of data needs further phenotypic assays of these pumps.

The role of chemotherapy drugs in the formation of resistant populations of mycobacterium tuberculosis

1980 ◽  
Vol 61 (5) ◽  
pp. 58
Author(s):  
O. A. Irtuganova
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Laboratory Strain ◽  
Chemotherapy Drugs ◽  
Lowenstein Jensen ◽  
Strain H37rv

The aim of the work was to select variants of mycobacterium tuberculosis with altered drug resistance under the influence of anti-tuberculosis drugs. The laboratory strain H37RV was selected by 15 passages of one colony on solid Lowenstein-Jensen medium. In the obtained genetically homogeneous variant of mycobacteria for 1012 individuals, there was not a single one resistant to rifampicin, isoniazid, streptomycin, ethionamide and ethambutol.

scholarly journals pH-Dependent Picosecond Structural Dynamics in the Distal Pocket of Nitrophorin 4 Investigated by 2D IR Spectroscopy

2013 ◽  
Vol 117 (49) ◽  
pp. 15804-15811 ◽  
Author(s):  
Mark Cheng ◽  
Jennifer F. Brookes ◽  
William R. Montfort ◽  
Munira Khalil
Keyword(s):  
Ir Spectroscopy ◽  
Structural Dynamics ◽  
2D Ir ◽  
Nitrophorin 4 ◽  
Ph Dependent

2D-IR spectroscopy: an additional dimension to investigate ultrafast structural dynamics

2013 ◽  
Vol 44 (10) ◽  
pp. 1470-1477 ◽  
Author(s):  
Manuela Lima ◽  
Marco Candelaresi ◽  
Paolo Foggi
Keyword(s):  
Ir Spectroscopy ◽  
Structural Dynamics ◽  
Additional Dimension ◽  
2D Ir
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