A multiple genome analysis of Mycobacterium tuberculosis reveals specific novel genes and mutations associated with pyrazinamide resistance

Autor: Ricardo Antiparra, Pilar Lizárraga, Basilio Cieza, Patricia Sheen, David Requena, Robert H. Gilman, Mirko Zimic, Arnab Pain, Louis Grandjean, Bryan Lucero, Ruth McNerney, Taane G. Clark, David Moore, Elisa Roncal, Eduardo Gushiken
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Resistance
Antitubercular Agents
Drug resistance
medicine.disease_cause
Genome
Genotype
MDR
Phylogeny
Genetics
Mutation
biology
Drugs
Drug Resistance
Bacterial/genetics
Genomics
3. Good health
PncA
Genes
Bacterial/genetics
Pyrazinamide/pharmacology
Mutations
Biotechnology
medicine.drug
Research Article
Tuberculosis
lcsh:QH426-470
lcsh:Biotechnology
030106 microbiology
Polymorphism
Single Nucleotide
Mycobacterium tuberculosis
03 medical and health sciences
lcsh:TP248.13-248.65
Drug Resistance
Bacterial
medicine
Antitubercular Agents/pharmacology
Efflux pump
Metallochaperone
Mycobacterium tuberculosis/drug effects/genetics
Pyrazinamide
biology.organism_classification
medicine.disease
lcsh:Genetics
030104 developmental biology
Genes
Genes
Bacterial
purl.org/pe-repo/ocde/ford#1.06.07 [https]
Zdroj: BMC Genomics
BMC Genomics, Vol 18, Iss 1, Pp 1-11 (2017)
ISSN: 1471-2164
Popis: Background Tuberculosis (TB) is a major global health problem and drug resistance compromises the efforts to control this disease. Pyrazinamide (PZA) is an important drug used in both first and second line treatment regimes. However, its complete mechanism of action and resistance remains unclear. Results We genotyped and sequenced the complete genomes of 68 M. tuberculosis strains isolated from unrelated TB patients in Peru. No clustering pattern of the strains was verified based on spoligotyping. We analyzed the association between PZA resistance with non-synonymous mutations and specific genes. We found mutations in pncA and novel genes significantly associated with PZA resistance in strains without pncA mutations. These included genes related to transportation of metal ions, pH regulation and immune system evasion. Conclusions These results suggest potential alternate mechanisms of PZA resistance that have not been found in other populations, supporting that the antibacterial activity of PZA may hit multiple targets. Electronic supplementary material The online version of this article (10.1186/s12864-017-4146-z) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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