Genetic diversity of Mycobacterium tuberculosis isoniazid monoresistant and multidrug-resistant in Rio Grande do Sul, a tuberculosis high-burden state in Brazil

Esteves, Lainister de Oliveira; Costa, Elis Regina Dalla; Vasconcellos, Sidra Ezídio Gonçalves; Vargas, Andrei; Ferreira, Sérgio Luis Montego; Halon, Maria Laura; Ribeiro, Marta Osório; Rodenbusch, Rodrigo; Gomes, Harrison Magdinier; Suffys, Philip Noël; Rossetti, Maria Lúcia Rosa

doi:10.1016/j.tube.2018.02.009

Cited by 17 publications

(15 citation statements)

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“…By sequencing the kat G gene, mutations in 106 of our isolates (80.9%) at 315 codons were observed, agreeing also with other studies from the same state [ 22 ] and other regions [ 4 ]. Regarding the inh A gene, 41 MDR M.tb isolates (31.3%) had mutation in the promoter region of the gene.…”

Section: Discussionsupporting

confidence: 92%

“…In the analysis of the rpo B gene, the most frequent mutations found were in the 531, 516 and 526 codons, the same as reported in other studies with RIF-resistant isolates [ 22 , 28 ]. The mutation in the codon 531 stands out with higher frequency (61.8%), also found in other studies in the same state [ 22 , 29 ], in other regions of Brazil [ 30 , 31 ] and other countries [ 28 ]. The codon 516 in the rpo B gene was mutated in 16.8% of the isolates and 2.3% of them had single nucleotide exchange, other studies show a bigger mutation rate with SNP in this codon [ 30 , 32 ].…”

Section: Discussionsupporting

confidence: 78%

“…It was observed in 19/131 (14.5%) of our samples, and a similar frequency was also found by Esteves et al . [ 22 ] in a similar study in the same region of Brazil. According to Esteves et al .…”

Section: Discussionmentioning

confidence: 84%

“…Regarding the inh A gene, 41 MDR M.tb isolates (31.3%) had mutation in the promoter region of the gene. The frequency of mutations related to the inh A gene varies from different places [ 23 ], even when compared to sampling from the same region [ 22 ]. In this study, we did not find mutation on −17 position, as described recently in the same state [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

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Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

et al. 2019

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Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

et al. 2019

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“…Furthermore, the treatment outcome is most likely unfavorable and failure to identify an INH-resistant isolate is equivalent to losing the efficacy of one of the drugs and compromising the basic regimen of treatment. (17) The lack of adequate treatment to combat an INH resistant isolate could also be inducing gene-level changes (mutations), generating MDR clones, since resistance to RIF comes in sequence. (2) The qPCR assays performed in this study identified the most known mutations in genetic regions associated with INH resistance (katG 315 G/C and inhA -15 C/T; GenBank: (MG995339, MG995338, MG995265 e CP023597 -National Centre for Biotechnology Information -NCBIhttps: //www.ncbi.…”

Section: Discussionmentioning

confidence: 99%

Rapid detection of Mycobacterium tuberculosis DNA and genetic markers for Isoniazid resistance in Ziehl-Neelsen stained slides

Bello

Morais

Jesus

et al. 2020

Mem. Inst. Oswaldo Cruz

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BACKGROUND Early diagnosis of tuberculosis (TB) and identification of strains of Mycobacterium tuberculosis resistant to anti-TB drugs are considered the main factors for disease control. OBJECTIVES To standardise a real-time polymerase chain reaction (qPCR) assay technique and apply it to identify mutations involved in M. tuberculosis resistance to Isoniazid (INH) directly in Ziehl-Neelsen (ZN) stained slides. METHODS Were analysed 55 independent DNA samples extracted from clinical isolates of M. tuberculosis by sequencing. For application in TB diagnosis resistance, 59 ZN-stained slides were used. The sensitivity, specificity and Kappa index, with a 95% confidence interval (CI95%), were determined. FINDINGS The agreement between the tests was, for the katG target, the Kappa index of 0.89 (CI95%: 0.7-1.0). The sensitivity and specificity were 97.6% (CI95%: 87.7-99.9) and 91.7% (CI95%: 61.5-99.5), respectively. For inhA, the Kappa index was 0.92 (CI95%: 0.8-1.0), the sensitivity and specificity were 94.4% (CI95%: 72.7-99.8) and 97.3% (CI95%: 85.8-99.9), respectively. The use of ZNstained slides for drug-resistant TB detection showed significant results when compared to other standard tests for drug resistance. MAIN CONCLUSIONS qPCR genotyping proved to be an efficient method to detect genes that confer M. tuberculosis resistance to INH. Thus, qPCR genotyping may be an alternative instead of sequencing.

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Spread of Mycobacterium tuberculosis in Southern Brazilian persons deprived of liberty: a molecular epidemiology study

Busatto

Possuelo

Bierhals

et al. 2023

Eur J Clin Microbiol Infect Dis

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Genetic diversity of Mycobacterium tuberculosis isoniazid monoresistant and multidrug-resistant in Rio Grande do Sul, a tuberculosis high-burden state in Brazil

Cited by 17 publications

References 64 publications

Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

Molecular characterisation of multidrug-resistantMycobacterium tuberculosisisolates from a high-burden tuberculosis state in Brazil

Rapid detection of Mycobacterium tuberculosis DNA and genetic markers for Isoniazid resistance in Ziehl-Neelsen stained slides

Spread of Mycobacterium tuberculosis in Southern Brazilian persons deprived of liberty: a molecular epidemiology study

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