Convergent evolution and topologically disruptive polymorphisms among multidrug-resistant tuberculosis in Peru

Autor: Sharon J. Peacock, Claudio U. Köser, M. Estee Török, Jorge Coronel, Mirko Zimic, Caroline Colijn, Diepreye Ayabina, Robert H. Gilman, David Moore, Louis Grandjean, Christophe Fraser, Julian Parkhill, Simon R. Harris, Michelle Kendall, Tomatada Iwamoto
Přispěvatelé: Engineering & Physical Science Research Council (EPSRC), Mokrousov, I, Grandjean, Louis [0000-0002-1457-8327], Iwamoto, Tomatada [0000-0002-2650-0308], Köser, Claudio U [0000-0002-0232-846X], Török, M Estee [0000-0001-9098-8590], Harris, Simon [0000-0003-1512-6194], Parkhill, Julian [0000-0002-7069-5958], Peacock, Sharon J [0000-0002-1718-2782], Colijn, Caroline [0000-0001-6097-6708], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
Bacterial Diseases
Male
0301 basic medicine
Extensively Drug-Resistant Tuberculosis
Plant Science
Plant Roots
Biochemistry
Genome
0302 clinical medicine
Drug Resistance
Multiple
Bacterial
Peru
Tuberculosis
Multidrug-Resistant
Medicine and Health Sciences
Phylogeny
Data Management
Genetics
Immune System Proteins
Multidisciplinary
biology
Phylogenetic tree
Plant Anatomy
Phylogenetic Analysis
3. Good health
Phylogenetics
Actinobacteria
Infectious Diseases
Medicine
Female
Research Article
Adult
Computer and Information Sciences
General Science & Technology
Science
Immunology
Single-nucleotide polymorphism
Microbiology
Polymorphism
Single Nucleotide
Mycobacterium tuberculosis
Young Adult
03 medical and health sciences
Microbial Control
MD Multidisciplinary
Tuberculosis
Multidrug-Resistant/microbiology
medicine
Tuberculosis
Humans
Evolutionary Systematics
Gene
Taxonomy
Pharmacology
Evolutionary Biology
Bacteria
Organisms
Mycobacterium tuberculosis/drug effects/genetics
Biology and Life Sciences
Proteins
Extensively drug-resistant tuberculosis
Tropical Diseases
biology.organism_classification
medicine.disease
Root Structure
Drug Resistance
Multiple
Bacterial/genetics
030104 developmental biology
Genes
Bacterial
purl.org/pe-repo/ocde/ford#3.02.07 [https]
Antibiotic Resistance
Mutation
Epistasis
Antimicrobial Resistance
030217 neurology & neurosurgery
Zdroj: e0189838
PLoS ONE, Vol 12, Iss 12, p e0189838 (2017)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0189838
Popis: Background Multidrug-resistant tuberculosis poses a major threat to the success of tuberculosis control programs worldwide. Understanding how drug-resistant tuberculosis evolves can inform the development of new therapeutic and preventive strategies. Methods Here, we use novel genome-wide analysis techniques to identify polymorphisms that are associated with drug resistance, adaptive evolution and the structure of the phylogenetic tree. A total of 471 samples from different patients collected between 2009 and 2013 in the Lima suburbs of Callao and Lima South were sequenced on the Illumina MiSeq platform with 150bp paired-end reads. After alignment to the reference H37Rv genome, variants were called using standardized methodology. Genome-wide analysis was undertaken using custom written scripts implemented in R software. Results High quality homoplastic single nucleotide polymorphisms were observed in genes known to confer drug resistance as well as genes in the Mycobacterium tuberculosis ESX secreted protein pathway, pks12, and close to toxin/anti-toxin pairs. Correlation of homoplastic variant sites identified that many were significantly correlated, suggestive of epistasis. Variation in genes coding for ESX secreted proteins also significantly disrupted phylogenetic structure. Mutations in ESX genes in key antigenic epitope positions were also found to disrupt tree topology. Conclusions Variation in these genes have a biologically plausible effect on immunogenicity and virulence. This makes functional characterization warranted to determine the effects of these polymorphisms on bacterial fitness and transmission.
Databáze: OpenAIRE
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