scholarly journals Clade-Specific Distribution of Antibiotic Resistance Mutations in the Population of Mycobacterium tuberculosis - Prospects for Drug Resistance Reversion

2018 ◽  
Author(s):  
Karen van Niekerk ◽  
Rian Pierneef ◽  
Oleg N. Reva ◽  
Ilya S. Korostetskiy ◽  
Aleksandr I. Ilin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Resistance Mutations ◽  
Specific Distribution ◽  
Antibiotic Resistance Mutations

scholarly journals Predicting nitroimidazole antibiotic resistance mutations in Mycobacterium tuberculosis with protein engineering

2020 ◽  
Vol 16 (2) ◽  
pp. e1008287 ◽  
Author(s):  
Brendon M. Lee ◽  
Liam K. Harold ◽  
Deepak V. Almeida ◽  
Livnat Afriat-Jurnou ◽  
Htin Lin Aung ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Protein Engineering ◽  
Resistance Mutations ◽  
Antibiotic Resistance Mutations

scholarly journals Predicting nitroimidazole antibiotic resistance mutations in Mycobacterium tuberculosis with protein engineering

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Brendon Lee ◽  
Deepak Almeida ◽  
Livnat Afriat-Jurnou ◽  
Htin Aung ◽  
Brian Forde ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Protein Engineering ◽  
Resistance Mutations ◽  
Antibiotic Resistance Mutations

scholarly journals Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis

2018 ◽  
Author(s):  
Joshua L. Payne ◽  
Fabrizio Menardo ◽  
Andrej Trauner ◽  
Sonia Borrell ◽  
Sebastian M. Gygli ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Dna Sequence ◽  
Adaptive Evolution ◽  
Gene Promoters ◽  
Human Pathogen ◽  
Resistance Mutations ◽  
Resistance Evolution ◽  
Transition Bias ◽  
Antibiotic Resistance Mutations

AbstractTransition bias, an overabundance of transitions relative to transversions, has been widely reported among studies of mutations spreading under relaxed selection. However, demonstrating the role of transition bias in adaptive evolution remains challenging. We addressed this challenge by analyzing adaptive antibiotic-resistance mutations in the major human pathogen Mycobacterium tuberculosis. We found strong evidence for transition bias in two independently curated datasets comprising 152 and 208 antibiotic resistance mutations. This was true at the level of mutational paths (distinct, adaptive DNA sequence changes) and events (individual instances of the adaptive DNA sequence changes), and across different genes and gene promoters conferring resistance to a diversity of antibiotics. It was also true for mutations that do not code for amino acid changes (in gene promoters and the ribosmal gene rrs), and for mutations that are synonymous to each other and are therefore likely to have similar fitness effects, suggesting that transition bias can be caused by a bias in mutation supply. These results point to a central role for transition bias in determining which mutations drive adaptive antibiotic resistance evolution in a key pathogen.Significance statementWhether and how transition bias influences adaptive evolution remain open questions. We studied 296 DNA mutations that confer antibiotic resistance to the human pathogen Mycobacterium tuberculosis. We uncovered strong transition bias among these mutations and also among the number of times each mutation has evolved in different strains or geographic locations, demonstrating that transition bias can influence adaptive evolution. For a subset of mutations, we were able to rule out an alternative selection-based hypothesis for this bias, indicating that transition bias can be caused by a biased mutation supply. By revealing this bias among M. Tuberculosis resistance mutations, our findings improve our ability to predict the mutational pathways by which pathogens overcome treatment.

scholarly journals Antibiotic Resistance and Single-Nucleotide Polymorphism Cluster Grouping Type in a Multinational Sample of Resistant Mycobacterium tuberculosis Isolates

2007 ◽  
Vol 51 (11) ◽  
pp. 4157-4159 ◽  
Author(s):  
M. Brimacombe ◽  
M. Hazbon ◽  
A. S. Motiwala ◽  
D. Alland
Keyword(s):  
Drug Resistance ◽  
Single Nucleotide Polymorphism ◽  
Antibiotic Resistance ◽  
Mycobacterium Tuberculosis ◽  
Classification System ◽  
Resistance Mutations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Cluster Grouping ◽  
Evolutionary Lineages

ABSTRACT A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had higher proportions of katG codon 315 mutations and resistance to four drugs.

scholarly journals The fitness costs of antibiotic resistance mutations

2014 ◽  
Vol 8 (3) ◽  
pp. 273-283 ◽  
Author(s):  
Anita H. Melnyk ◽  
Alex Wong ◽  
Rees Kassen
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mutations ◽  
Fitness Costs ◽  
Antibiotic Resistance Mutations

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.

Antibiotic resistance mutations induced in growing cells of Bacillus-related thermophiles

2018 ◽  
Vol 71 (3) ◽  
pp. 382-389 ◽  
Author(s):  
Hirokazu Suzuki ◽  
Tatsunari Taketani ◽  
Jyumpei Kobayashi ◽  
Takashi Ohshiro
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Mutations ◽  
Antibiotic Resistance Mutations
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