Molecular profiling of drug resistant isolates of Mycobacterium tuberculosis in the state of Santa Catarina, southern Brazil

Prim, Rodrigo Ivan; Schörner, Marcos André; Senna, Simone Gonçalves; Nogueira, Christiane Lourenço; Figueiredo, Anna Carolina Cançado; Oliveira, Jaquelline Germano de; Rovaris, Darcita Bürger; Bazzo, Maria Luiza

doi:10.1590/0074-02760150100

Cited by 20 publications

(13 citation statements)

References 32 publications

(39 reference statements)

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“…The Euro-American lineage predominance in Santa Catarina State and in the Southern Brazil 17 , 34 , occurred due to migratory processes from Europe to South America that increased in the seventeenth century 35 . Therefore, LAM, T and Haarlem, the most common spoligotyping families identified in this study, were also found in other studies in Southern Brazil 17 , 20 , 34 , 36 , 37 . Our examination of the distribution of the fbpC 103 SNP, considered as a highly specific marker for the LAM family not only confirmed the identification of all spoligotyping-based identified LAM, but increased the frequency of this lineage to 69.5% (105/151).…”

Section: Discussionsupporting

confidence: 88%

“…This study evaluates the scenario of M.tb strain diversity between May-2014 and May-2016, analyzing individuals from the metropolitan region of Florianópolis diagnosed with pulmonary TB at Florianópolis and São José (the two most populous of the 22 cities that comprise the metropolitan region of Florianópolis). Despite the importance of knowing the molecular profile of circulating M.tb strains in a given setting, the existing data for this particular region is limited to the classical genotypic characterization of circulating strains 17,18,20 . The present study comprises the first genome-wide study on M.tb in Santa Catarina state.…”

Section: Discussionmentioning

confidence: 99%

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Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

Verza

Scheffer

Salvato

et al. 2020

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Mycobacterium tuberculosis (M.tb), the pathogen responsible for tuberculosis (TB) poses as the major cause of death among infectious diseases. The knowledge about the molecular diversity of M.tb enables the implementation of more effective surveillance and control measures and, nowadays, Whole Genome Sequencing (WGS) holds the potential to produce high-resolution epidemiological data in a high-throughput manner. Florianópolis, the state capital of Santa Catarina (SC) in south Brazil, shows a high TB incidence (46.0/100,000). Here we carried out a WGS-based evaluation of the M.tb strain diversity, drug-resistance and ongoing transmission in the capital metropolitan region. Resistance to isoniazid, rifampicin, streptomycin was identified respectively in 4.0% (n = 6), 2.0% (n = 3) and 1.3% (n = 2) of the 151 studied strains by WGS. Besides, resistance to pyrazinamide and ethambutol was detected in 0.7% (n = 1) and reistance to ethionamide and fluoroquinolone (FQ) in 1.3% (n = 2), while a single (0.7%) multidrug-resistant (MDR) strain was identified. SNP-based typing classified all isolates into M.tb Lineage 4, with high proportion of sublineages LAM (60.3%), T (16.4%) and Haarlem (7.9%). The average core-genome distance between isolates was 420.3 SNPs, with 43.7% of all isolates grouped across 22 genomic clusters thereby showing the presence of important ongoing TB transmission events. Most clusters were geographically distributed across the study setting which highlights the need for an urgent interruption of these large transmission chains. The data conveyed by this study shows the presence of important and uncontrolled TB transmission in the metropolitan area and provides precise data to support TB control measures in this region.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

Verza

Scheffer

Salvato

et al. 2020

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“…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: 85%

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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“…Ser531Leu was the most prevalent mutation found in rpoB among the MDR-TB isolates in this study (Table 4). These results are consistent with what has been observed by similar studies (Hillemann et al 2005;Poudel et al 2012;Prim et al 2015;San et al 2018). On the contrary, Lipin et al (2007) reported unusual findings of the predominance of the Asp516Val mutation (75%) among the LAM family in Russia.…”

Section: Frequencies Of Rpob Drug Resistance-conferring Mutations Amosupporting

confidence: 94%

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Solo

Suzuki

Kaile

et al. 2021

International Journal of Infectious Diseases

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The burden of multidrug-resistant tuberculosis (MDR-TB) has been reported to be increasing in Zambia. The reasons for the increase are still unclear. This study determined the diversity of Mycobacterium tuberculosis genotypes among isolates in Lusaka, the capital city, and investigated their association with MDR-TB. Methods: Spoligotyping, large sequence polymorphism (LSP) analysis, and sequencing of MDR associated genes were performed on a total of 274 M. tuberculosis clinical isolates stored at the University Teaching Hospital from 2013 to 2017. Of these, 134 were MDR-TB while 126 were pan-susceptible. Results: Spoligotyping showed the LAM family as the most predominant genotype (149/274, 54.4%) followed by the CAS family (44/274, 16.1%), T family (39/274, 14.2%), and minor proportions of X, S, Harleem, EAI and Beijing spoligofamilies were identified. Three M. bovis isolates were also observed. Among those, CAS1-Kili (SIT 21) and LAM1 (SIT 20) subfamilies showed a propensity for MDR-TB with p = 0.0001 and p = 0.001, respectively. Conclusions: This phenomenon might explain the future increase in the MDR-TB burden caused by specific lineages in Zambia. Therefore, it is recommended that the National TB control program in the country complements conventional control strategies with molecular analysis for monitoring and surveillance of MDR-TB epidemiology.

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Molecular profiling of drug resistant isolates of Mycobacterium tuberculosis in the state of Santa Catarina, southern Brazil

Cited by 20 publications

References 32 publications

Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

Genomic epidemiology of Mycobacterium tuberculosis in Santa Catarina, Southern Brazil

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

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

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