Catalogue Of Mutations In Mycobacterium Tuberculosis Complex And Their Association With Drug Resistance
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Catalogue Of Mutations In Mycobacterium Tuberculosis Complex And Their Association With Drug Resistance
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Author : World Health Organization
language : en
Publisher: World Health Organization
Release Date : 2023-11-14
Catalogue Of Mutations In Mycobacterium Tuberculosis Complex And Their Association With Drug Resistance written by World Health Organization and has been published by World Health Organization this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-11-14 with Medical categories.
Catalogue Of Mutations In Mycobacterium Tuberculosis Complex And Their Association With Drug Resistance
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Author :
language : en
Publisher: World Health Organization
Release Date : 2021-06-30
Catalogue Of Mutations In Mycobacterium Tuberculosis Complex And Their Association With Drug Resistance written by and has been published by World Health Organization this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-06-30 with Medical categories.
Exploring The Evolution Of Drug Resistance In Mycobacterium Using Whole Genome Sequencing Data
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Author : Dillon Muzondiwa
language : en
Publisher:
Release Date : 2019
Exploring The Evolution Of Drug Resistance In Mycobacterium Using Whole Genome Sequencing Data written by Dillon Muzondiwa and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
Mycobacterium tuberculosis (Mtb) remains a global challenge that has been worsened by the emergence of drug resistant strains of Mtb. We used publicly available Next Generation Sequencing (NGS) and drug susceptibility (DST) data to develop aÌ22́Ơ¿3Resistance snifferaÌ22́Ơ℗+, an online software program for the rapid prediction of lineage and Mtb drug resistance. Based on the distribution of polymorphisms in the genomes of Mtb, we calculated the power of association between the polymorphisms in different clades of Mtb and resistance to 13 anti-TB drugs. Our data suggests that the development of drug resistance in Mtb is a stepwise process that involves the accumulation of polymorphisms in the Mtb genome. We carefully curated the polymorphisms based on their association powers to create a diagnostic key that captures patterns of these polymorphisms that can be used to predict lineage and drug resistance in Mtb. This diagnosis key was incorporated into the Resistance Sniffer tool, an online software program that we developed for the rapid diagnosis of drug resistance in Mtb. The tool was tested using sequence data from the South Africa Medical Research Council (SA-MRC). Our data suggests that the majority of the strains in SA may have been brought by the arrival of European settlers while the more resistant strains may have been introduced in the region by Asian travellers later on. We next sought to determine non-random associations between polymorphic sites in genomes of Mtb. Using the attributable risk (Ra) statistical methods, we distinguished between functional associations and associations that may have been due to genetic drift events for different Mtb clades. We then integrated the (Ra) data with drug susceptibility and annotation data to generate networks in Cytoscape 3.71. These networks were then used to infer evolutionary trajectories that drive the emergence and fixation of the drug resistant phenotype in different clades of Mtb. We demonstrate that strains from the Lineage 1.2 are associated with less complex functional associations compared to the strains from other clades such as the Asian and Euro-American clades. Our data also shows that the predisposition of strains from the Asian clades to develop multi-drug resistance may be attributed to a complex network of functional interactions of mutations in genes that are involved in several aspects of Mtb physiology such as cell wall modelling, lipid metabolism, stress response and DNA repair.
Strain Variation In The Mycobacterium Tuberculosis Complex Its Role In Biology Epidemiology And Control
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Author : Sebastien Gagneux
language : en
Publisher: Springer
Release Date : 2017-11-06
Strain Variation In The Mycobacterium Tuberculosis Complex Its Role In Biology Epidemiology And Control written by Sebastien Gagneux and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-11-06 with Science categories.
Until about 10 years ago, the general view in the field was that Mycobacterium tuberculosis, the causative agent of human tuberculosis was a “clone” with insufficient natural sequence variation between clinical strains to be considered biologically and epidemiologically “relevant”. This view has now changed quite dramatically thanks to the –omics revolution, particularly the advent of next generation DNA sequencing. Large-scale comparative genomic studies over the last few years have revealed that M. tuberculosis clinical strains are more genetically diverse than appreciated previously. Moreover, an increasing number of experimental and epidemiological studies are showing that this genetic diversity also translates into important phenotypic variation. Taken together, these findings have led to a paradigm shift, such that currently phylogenetic diversity among M. tuberculosis clinical strains is being considered in the development of new tools to combat tuberculosis. The purpose of this book is to bring together a series of contributions from some of the most influential groups working on various aspects of M. tuberculosis diversity, and which through their work have contributed to the this paradigm shift. This includes authors focusing on the evolution of M. tuberculosis in relation to other members of the M. tuberculosis complex adapted to animals, the co-evolution between M. tuberculosis and humans, the phenotypic consequences of strains diversity both from an experimental and epidemiological point of view, the ecology and evolution of drug resistant tuberculosis, the diversity and evolution of the BCG vaccine strains, and the use of mathematical modelling to study strain diversity and drug resistance in human tuberculosis. No such book has ever been published, and given the paradigm shift described above, this book will be a valuable resource both for established researchers as well as new scientists, clinicians and public health officials joining the growing field of tuberculosis research.
Use Of Next Generation Sequencing Technologies For The Detection Of Mutations Associated With Drug Resistance In Mycobacterium Tuberculosis Complex Technical Guide
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Author : world health organization
language : en
Publisher:
Release Date : 2022
Use Of Next Generation Sequencing Technologies For The Detection Of Mutations Associated With Drug Resistance In Mycobacterium Tuberculosis Complex Technical Guide written by world health organization and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022 with categories.
Identification Of Multiple And Novel Drug Resistance In Mycobacterium Tuberculosis Utilizing Protein Protein Interaction Networks
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Author :
language : en
Publisher:
Release Date : 2018
Identification Of Multiple And Novel Drug Resistance In Mycobacterium Tuberculosis Utilizing Protein Protein Interaction Networks written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with Electronic books categories.
Mycobacterium tuberculosis (Mtb) is one of the deadliest diseases. While antibiotics exist to treat it, their efficacy has waned in recent years due to drug-resistant strains of the bacteria. While there are methods to detect drug resistance in Mtb, there are potentially mutations which the bacteria harbor that could explain multiple resistances simultaneously, as well as explain novel mechanisms of drug resistance. Towards the identification of multiple and novel drug resistance mutations in Mtb, we analyzed the results of whole genome sequencing for 5,958 Mtb isolates using a three-part approach. We used the protein-protein interaction network for Mtb in the STRING database to identify mutant proteins which were incident to two, or once removed from being incident to two proteins from an original protein set known to cause drug resistance in the bacteria in part one. In the second part, the set of starting proteins was changed to include any two mutated proteins between two isolates with unknown drug resistance to a certain antibiotic. In the last part, the entire network was clustered using an algorithm SPICi, and the most mutated clusters in unknown resistance isolates were determined and functionally characterized using Gene Ontology terms. The proteins which most commonly appeared between double-resistant isolates were GrcC2, associated with isoprenoid biosynthesis in aminoglycoside and pyrazinamide resistance. Mutations in proteins associated with ESX secretion systems were found to correlate to fluoroquinolone single resistance. When using a set of all mutated proteins between two drug resistant isolates, many hypothetical genes were identified as potentially important, however they normally have ill-defined functional roles. The most mutated cluster in drug resistant isolates included PE_PGRS49 and PE_PGRS50, both part of a grouping of proteins in Mtb called PE/PPE proteins which also have murky functional annotation. The other most represented clusters were heavy in lipid metabolism, and also vitamin metabolism, which could be an interesting initiating point for future studies. Overall, the results of this study were exploratory, with mostly poor correlation and low sensitivity and specificity. If experimentally validated, the multiple and novel mechanisms of drug resistance identified herein may be corroborated.
Molecular Epidemiology Study Of Mycobacterium Tuberculosis Complex
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Author : Yogendra Shah
language : en
Publisher: BoD – Books on Demand
Release Date : 2021-09-15
Molecular Epidemiology Study Of Mycobacterium Tuberculosis Complex written by Yogendra Shah and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021-09-15 with Medical categories.
Tuberculosis (TB), which is caused by the infectious agent Mycobacterium tuberculosis (MTB), is a major global public health problem that infects one third of the world’s population. This book provides an overview of the molecular epidemiology pattern, transmission dynamics, host response, evolution, and pathogenesis mechanisms of TB. Chapters explore such topics as mechanisms associated with increasing trends of drug-resistant TB, the development of anti-mycobacterial drugs, genotyping tools, diagnosis and treatment of latent tuberculosis infection, and more.
Laboratory Methods For Clinical And Public Health
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Author : George P. Kubica
language : en
Publisher:
Release Date : 1967
Laboratory Methods For Clinical And Public Health written by George P. Kubica and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1967 with Medical bacteriology categories.
Mutation And Methylation Mechanisms Of Rifampicin Resistance In Mycobacterium Tuberculosis
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Author :
language : en
Publisher:
Release Date : 2016
Mutation And Methylation Mechanisms Of Rifampicin Resistance In Mycobacterium Tuberculosis written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Electronic books categories.
Rifampicin (RIF) is a first-line drug used to treat Mycobacterium tuberculosis (Mtb). Resistance to RIF is predominantly associated with chromosomal mutations in the rpoB gene. This study sought to determine the mutations that explained RIF resistance in a set of 347 isolates (303 resistant, 44 susceptible). The promoter regions of three efflux pump genes, emrB, pstB, and drrA, were also examined for mutations that may confer RIF resistance. Eight RIF-resistant isolates lacked genetic explanation for their resistance but had good sequencing coverage, and eight RIF-susceptible isolates contained mutations reported to confer resistance to RIF. The lack of explanation for the resistance of several isolates raises the questions as to whether current diagnostic methods are reliable enough to detect low-level resistance to rifampicin, and whether there are other mechanisms of resistance that are not yet fully understood. For this reason, the DNA methylation patterns of our isolates, especially those lacking explanation, were examined for associations that would provide insight into other potential mechanisms of resistance. It was found that the unexplained RIF-R isolates had methylation patterns that were comparable to reported drug-tolerant populations, and lacked methylation of several drug effluxing pump genes, suggesting a possible combination of both drug tolerance and (over)expression of efflux pumps as a potential mechanism of resistance. The mechanisms of drug resistance in Mtb maybe more dynamic than currently presumed, and the common mechanism of genetic mutation may eventually be outcompeted by a more adaptive and virulent population of Mtb that is able to respond to a changing environment more quickly. This includes the more immediate benefits that might result from both drug effluxing and the control of gene expression via methylation (which may contribute to the potential for drug tolerance); both of these mechanisms may allow the bacteria to survive long enough to either develop more permanent solutions like genetic mutations or to persist in the presence of the drug during the treatment period. Though these conclusions are daunting, they may provide a more robust picture of the evolution and adaptation of Mtb that could help prevent the exacerbation of drug resistance in the future.
Drug Resistance In Mycobacterium Tuberculosis
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Author : Katia Peñuelas-Urquides
language : en
Publisher:
Release Date : 2018
Drug Resistance In Mycobacterium Tuberculosis written by Katia Peñuelas-Urquides and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with Medicine categories.
Tuberculosis (TB) remains to be a serious health problem worldwide. There is an increased transmission of Mycobacterium tuberculosis strains with drug resistance, hence complicating TB control. The deciphering of the M. tuberculosis genome, together with the implementation of new molecular biology tools, has allowed the identification of changes in nucleic acid sequences with a functional impact. These mutations have become important in the design of early-diagnostic kits to identify the resistance profile of M. tuberculosis. Since the conventional methods to determine the identity of M. tuberculosis strains based in cultures are laborious, time-consuming and performed by specialized technicians, the result is generated until 4 months after receiving the samples. During this time, patients with TB are not adequately treated, and resistant strains may be transmitted to the rest of the population. In this chapter, we describe the most relevant mutations in genes associated with drug resistance in M. tuberculosis, the analysis of gene expression to identify new markers of drug resistance strains, and the development of new antituberculosis drugs against drug-resistant strains.