Mycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Fonseca, Leila de Souza
Marsico, Anna Grazia
de Oliveira Vieira, Gisele Betzler
Sobral, Luciana Fonseca
Saad, Maria Helena Féres
MetadataShow full item record
AbstractIt has been widely accepted, that pyrazinamide (PZA) resistance in Mycobacterium tuberculosis is correlated with mutations in the pncA gene. But since years researchers have been puzzled by the fact that up to 30% of PZA resistant strains do not show any correlation between PZA resistance and mutations in the pncA gene, and thus may vary with geographic area. The objective of the study was to investigate the correlation between PZA susceptibility and mutations in pncA gene in M. tuberculosis isolates from individuals living in a highly endemic area. Therefore we analyzed drug resistant and multidrug resistant (MDR) isolates from patients in Rio de Janeiro, Brazil. From a total of 97 clinical isolates of M. tuberculosis 35 were identified as PZA resistant, 24/35 strains did not show PZase activity and 15/24 (62.5%) strains possess mutation in the pncA gene. This is a low correlation between PZA resistance and PZase activity (68.6%) and even lower correlation between PZA resistance and the presence of mutation in pncA gene (45.7%). Most of the mutations found were conserved near the active site or metal binding site of PZase. The 146A>C mutation was found both in PZA resistant and susceptible isolates, suggesting that this mutation may not fully associated with PZA resistance. Of the mutations found, three have not been previously described. The insertions 192-193 TCCTCGTC and 388-389 AGGTCGATG, although found before, here was found to be a short tandem repeat and in one strain, insertion of the IS6110 was observed 55nt upstream of the gene. All PZA resistant isolates had no mutation in the gene coding ribosomal protein S1 (rpsA), which has recently been proposed as alternate target for pyrazinoic acid (POA). The results show a low association of PZA resistance and pncA gene mutations in a selected patient group from an highly endemic area. Our findings point out that the phenotypic susceptibility testing remains important for the detection of PZA-resistant M. tuberculosis.
CitationMycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene. 2013, 19C:1-6 Infect. Genet. Evol.
AffiliationDepartment of Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
JournalInfection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
The following license files are associated with this item:
- [Characteristics of pncA gene in multidrug-resistant Mycobacterium tuberculosis isolates and its correlation with drug resistance to pyrazinamide].
- Authors: Hong CY, Wang F, Gui J, Liu XL
- Issue date: 2012 May
- Genetic and phenotypic characterization of pyrazinamide-resistant mycobacterium tuberculosis complex isolates in Japan.
- Authors: Miyagi C, Yamane N, Yogesh B, Ano H, Takashima T
- Issue date: 2004 Feb
- Mutations in the pncA and rpsA genes among 77 Mycobacterium tuberculosis isolates in Kazakhstan.
- Authors: Akhmetova A, Kozhamkulov U, Bismilda V, Chingissova L, Abildaev T, Dymova M, Filipenko M, Ramanculov E
- Issue date: 2015 Feb
- Pyrazinamide resistance and mutations in pncA among isolates of Mycobacterium tuberculosis from Khyber Pakhtunkhwa, Pakistan.
- Authors: Khan MT, Malik SI, Ali S, Masood N, Nadeem T, Khan AS, Afzal MT
- Issue date: 2019 Feb 6
- Non-pncA Gene-Mutated but Pyrazinamide-Resistant Mycobacterium tuberculosis: Why Is That?
- Authors: Werngren J, Alm E, Mansjö M
- Issue date: 2017 Jun