Mycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene.

2.50
Hdl Handle:
http://hdl.handle.net/10033/298902
Title:
Mycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene.
Authors:
Bhuju, Sabin; Fonseca, Leila de Souza; Marsico, Anna Grazia; de Oliveira Vieira, Gisele Betzler; Sobral, Luciana Fonseca; Stehr, Matthias; Singh, Mahavir; Saad, Maria Helena Féres
Abstract:
It 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.
Affiliation:
Department of Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Citation:
Mycobacterium 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.
Journal:
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
Issue Date:
14-Jun-2013
URI:
http://hdl.handle.net/10033/298902
DOI:
10.1016/j.meegid.2013.06.008
PubMed ID:
23770140
Type:
Article
ISSN:
1567-7257
Appears in Collections:
publications of the research group genomeanalytics (GMAK)

Full metadata record

DC FieldValue Language
dc.contributor.authorBhuju, Sabinen_GB
dc.contributor.authorFonseca, Leila de Souzaen_GB
dc.contributor.authorMarsico, Anna Graziaen_GB
dc.contributor.authorde Oliveira Vieira, Gisele Betzleren_GB
dc.contributor.authorSobral, Luciana Fonsecaen_GB
dc.contributor.authorStehr, Matthiasen_GB
dc.contributor.authorSingh, Mahaviren_GB
dc.contributor.authorSaad, Maria Helena Féresen_GB
dc.date.accessioned2013-08-15T13:28:21Z-
dc.date.available2013-08-15T13:28:21Z-
dc.date.issued2013-06-14-
dc.identifier.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.en_GB
dc.identifier.issn1567-7257-
dc.identifier.pmid23770140-
dc.identifier.doi10.1016/j.meegid.2013.06.008-
dc.identifier.urihttp://hdl.handle.net/10033/298902-
dc.description.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.en_GB
dc.languageENG-
dc.rightsArchived with thanks to Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseasesen_GB
dc.titleMycobacterium tuberculosis isolates from Rio de Janeiro reveal unusually low correlation between pyrazinamide resistance and mutations in the pncA gene.-
dc.typeArticleen
dc.contributor.departmentDepartment of Genome Analytics, Helmholtz Centre for Infection Research, Braunschweig, Germany.en_GB
dc.identifier.journalInfection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseasesen_GB

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