Characteristics of multidrug-resistant Mycobacterium tuberculosis in southern Brazil

Perizzolo, Paulo Fernado; Costa, Elis Regina Dalla; Ribeiro, Andrezza; Spies, Fernanda Sá; Ribeiro, Marta Osório; Dias, Claudia; Unis, Gisela; Silva, Pedro Eduardo Almeida da; Gomes, Harrison Magdinier; Suffys, Philip Noël; Rossetti, Maria Lúcia Rosa

doi:10.1016/j.tube.2011.09.008

Cited by 33 publications

(41 citation statements)

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“…Earlier outbreaks of MDR strains have been reported in the city of Porto Alegre, including a LAM5 strain reported by Perizzolo et al (18) and a recent MDR-TB LAM2 strain (57), both being of the RD Rio genotype; the nine isolates described here, however, were not of the RD Rio genotype. This work further reinforces the extreme care needed to be taken when using databases for comparisons of genotype identifications of local M. tuberculosis isolates, and it highlights the need to use multiple markers for correct species and/or lineage assignation of isolates with infrequent spoligotypes.…”

Section: Discussionsupporting

confidence: 42%

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

et al. 2015

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We recently detected the spoligotype patterns of strains of Mycobacterium pinnipedii, a species of the Mycobacterium tuberculosis complex, in sputum samples from nine cases with pulmonary tuberculosis residing in Porto Alegre, South Brazil. Because this species is rarely encountered in humans, we further characterized these nine isolates by additional genotyping techniques, including 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, verification of the loci TbD1, RD9, pks15/1, RD Rio , and fbpC, the insertion of IS6110 at a site specific to the M. tuberculosis Latin American Mediterranean (LAM) lineage, and whole-genome sequencing. The combined analysis of these markers revealed that the isolates are in fact M. tuberculosis and more specifically belong to the LAM genotype. Most of these isolates (n ‫؍‬ 8) were shown to be multidrug resistant (MDR), which prompted us to perform partial sequencing of the rpoA, rpoB, rpoC, katG, and inhA genes. Seven isolates (77.8%) carried the S315T mutation in katG, and one of these (11%) also presented the C(؊17)T single-nucleotide polymorphism (SNP) in inhA. Interestingly, six of the MDR isolates also presented an undescribed insertion of 12 nucleotides (CCA GAA CAA CCC) in codon 516 of rpoB. No putative compensatory mutation was found in either rpoA or rpoC. This is the first report of an M. tuberculosis LAM family strain with a convergent M. pinnipedii spoligotype. These spoligotypes are observed in genotype databases at a modest frequency, highlighting that care must be taken when identifying isolates in the M. tuberculosis complex on the basis of single genetic markers. M. tuberculosis is the predominant cause of human TB worldwide, but M. africanum and M. bovis remain important agents of human disease in certain geographical regions (9). The MTBC species share identical 16S rRNA sequences, and recent studies have improved our knowledge on the genetic diversity, host range, epidemiological aspects, and differences in pathogenicity and virulence among the species of the complex (10, 11). Based on the various genotyping techniques, like spoligotyping (12), restriction fragment length polymorphism (RFLP) (13), mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing (14), and whole-genome sequencing (15), M. tuberculosis strains have been subdivided into lineages and families. The most geographically widespread family worldwide (spoligotyping) is the Latin American Mediterranean (LAM) lineage, which is part of the heterogeneous Euro-American lineage, one of seven M. tuberculosis lineages (16). The LAM family strains are widespread across all five continents, with a marked incidence in

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Section: Discussionsupporting

confidence: 42%

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

et al. 2015

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“…La ausencia de actividad catalasa, debida a mutaciones en el gen katG, codificante de esta enzima, constituye uno de los principales mecanismos de resistencia a HIN [12][13][14][15] . .…”

Section: Artículo Originalunclassified

“…La mayoría de los reportes sobre resistencia a HIN sugieren que las mutaciones katG S315T, conjuntamente con la mutación del promotor del gen inhA, explican la mayor parte de la resistencia a HIN, aun cuando en un pequeño porcentaje de cepas, la resistencia no puede atribuirse a alteraciones en la secuencia de estos genes 14,15,21,33 . Indudablemente, el estudio de susceptibilidad a HIN resulta complejo, debido a la heterogeneidad genética para el fenotipo de resistencia a este antimicrobiano; sin embargo, la mayoría de las investigaciones señalan que las mutaciones en el gen katG podría explicar aproximadamente entre 70 y 85% de la resistencia (Tabla 3), siendo de mayor importancia clínica, por inducir mayores niveles de resistencia a HIN 25,[34][35][36] .…”

Section: Artículo Originalunclassified

Detección de la mutación S315T en el gen katg como estrategia para identificación de Mycobacterium tuberculosis resistente a isoniacida en un laboratorio de referencia

Romay

Arraíz

Fuenmayor

et al. 2012

Rev. chil. infectol.

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“…A mutação responsável pela resistência a R ocorrem em um sítio chamado RDRR (região determinante de resistência à R) de 81pb, localizado entre os códons 507 e 533 do gene rpoB, sendo os códons 531 (Ser), 526 (His) e 526 (Asp) os principais locais de mutações (Hofling et al, 2005;Lipin et al, 2007;Gomes et al, 2012;Perizzolo et al, 2012). Essa mutação ocorre em 95-98% das cepas resistentes.…”

Section: Transferências Os Indicadores Distritais Se Aproximam Daqueunclassified

“…A mutação S315T1 foi a mutação mais frequente associada ao gene KatG concordando com estudos nacionais e internacionais (Silva et al, 2003Seifert et al, 2015. A mutação em inhA estava relacionada com mutações no códon 15 sendo esta mutação associada a cepas monorresistentes (Liu et al, 2015) Os resultados fenotípicos e genotípicos encontrados neste trabalho concordam com estudos nacionais e internacionais que apontam a vantagem decorrente da significativa redução do tempo para o diagnóstico da TB (Chikamatsu et al, 2011;Asencios et al, 2012;Perizzolo et al, 2012;Nosova et al, 2013).…”

Section: Transferências Os Indicadores Distritais Se Aproximam Daqueunclassified

Avaliação da resistência aos tuberculostáticos de primeira linha em cepas do complexo Mycobacterium Tuberculosis isolados no Distrito Federal

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Dedico este trabalho aos meus filhos Maria Eduarda e Vítor e ao meu afilhado Matheus, para que desde pequenos valorizem a importância dos estudos; ao meu marido Eduardo, pelo apoio incondicional; aos meus pais, que me permitiram chegar até aqui; à minha irmã Janay,pelo incentivo e por me substituir nas minhas ausências maternas e familiares; e à minha grande amiga Pérola -quem encontrou um amigo encontrou, no meu caso, uma Pérola. AGRADECIMENTOSA Deus, pelas tantas oportunidades que me proporcionou e por ter mе dado saúde е força para superar as dificuldades.Aos meus filhos, por entenderem todas as minhas ausências, eu peço perdão.Ao meu marido, por todas as noites não dormidas e por todas as infinitas formatações e correções gramaticais, a minha eterna gratidão.Aos meus pais, pelo amor, incentivo е apoio incondicionais.À minha orientadora, Professora Dra. Janeth de Oliveira Silva Naves, pela orientação, ensinamentos e confiança depositada durante todo este projeto.À Professora e amiga Dra.

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Characteristics of multidrug-resistant Mycobacterium tuberculosis in southern Brazil

Cited by 33 publications

References 13 publications

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

Multidrug-Resistant Mycobacterium tuberculosis of the Latin American Mediterranean Lineage, Wrongly Identified as Mycobacterium pinnipedii (Spoligotype International Type 863 [SIT863]), Causing Active Tuberculosis in South Brazil

Detección de la mutación S315T en el gen katg como estrategia para identificación de Mycobacterium tuberculosis resistente a isoniacida en un laboratorio de referencia

Avaliação da resistência aos tuberculostáticos de primeira linha em cepas do complexo Mycobacterium Tuberculosis isolados no Distrito Federal

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