Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil

Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a nat...

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Veröffentlicht in:PloS one 2014-08, Vol.9 (8), p.e104100-e104100
Hauptverfasser: de Freitas, Flávia A D, Bernardo, Vagner, Gomgnimbou, Michel K, Sola, Christophe, Siqueira, Hélio R, Pereira, Márcia A S, Fandinho, Fátima C O, Gomes, Harrison M, Araújo, Marcelo E I, Suffys, Philip N, Marques, Elizabeth A, Albano, Rodolpho M
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container_title PloS one
container_volume 9
creator de Freitas, Flávia A D
Bernardo, Vagner
Gomgnimbou, Michel K
Sola, Christophe
Siqueira, Hélio R
Pereira, Márcia A S
Fandinho, Fátima C O
Gomes, Harrison M
Araújo, Marcelo E I
Suffys, Philip N
Marques, Elizabeth A
Albano, Rodolpho M
description Multidrug resistance is a critical factor in tuberculosis control. To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center. Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates. Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.
doi_str_mv 10.1371/journal.pone.0104100
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Bernardo, Vagner ; Gomgnimbou, Michel K ; Sola, Christophe ; Siqueira, Hélio R ; Pereira, Márcia A S ; Fandinho, Fátima C O ; Gomes, Harrison M ; Araújo, Marcelo E I ; Suffys, Philip N ; Marques, Elizabeth A ; Albano, Rodolpho M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-5361778a6238d09d132937891c176e6960d82dd84802e9e4dd531e044b6344493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Antimicrobial agents</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Typing Techniques</topic><topic>Biology and life sciences</topic><topic>Brazil - epidemiology</topic><topic>Catalase - genetics</topic><topic>Chemotherapy</topic><topic>Cluster Analysis</topic><topic>Demography</topic><topic>DNA-Directed RNA Polymerases</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple, Bacterial - genetics</topic><topic>Enzymes</topic><topic>Epidemics</topic><topic>Female</topic><topic>Genes</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Incidence</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medicine and Health Sciences</topic><topic>Mortality</topic><topic>Multidrug resistance</topic><topic>Multidrug resistant organisms</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - classification</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - isolation &amp; 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To gain better understanding of multidrug resistant tuberculosis in Brazil, a retrospective study was performed to compare genotypic diversity and drug resistance associated mutations in Mycobacterium tuberculosis isolates from a national reference center. Ninety-nine multidrug resistant isolates from 12 Brazilian states were studied. Drug-resistance patterns were determined and the rpoB and katG genes were screened for mutations. Genotypic diversity was investigated by IS6110-RFLP and Luminex 47 spoligotyping. Mutations in rpoB and katG were seen in 91% and 93% of the isolates, respectively. Codon 315 katG mutations occurred in 82.8% of the isolates with a predominance of the Ser315Thr substitution. Twenty-five isolates were clustered in 11 groups with identical IS6110-RFLP patterns while 74 showed unique patterns with no association between mutation frequencies or susceptibility profiles. The most prevalent spoligotyping lineages were LAM (47%), T (17%) and Haarlen (12%). The Haarlen lineage showed a higher frequency of codon 516 rpoB mutations while codon 531 mutations prevailed in the other isolates. Our data suggest that there were no major multidrug resistant M. tuberculosis strains transmitted among patients referred to the reference center, indicating an independent acquisition of resistance. In addition, drug resistance associated mutation profiles were well established among the main spoligotyping lineages found in these Brazilian multidrug resistant isolates, providing useful data for patient management and treatment.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25093512</pmid><doi>10.1371/journal.pone.0104100</doi><oa>free_for_read</oa></addata></record>
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subjects Adult
Antimicrobial agents
Bacterial Proteins - genetics
Bacterial Typing Techniques
Biology and life sciences
Brazil - epidemiology
Catalase - genetics
Chemotherapy
Cluster Analysis
Demography
DNA-Directed RNA Polymerases
Drug resistance
Drug Resistance, Multiple, Bacterial - genetics
Enzymes
Epidemics
Female
Genes
HIV
Human immunodeficiency virus
Humans
Incidence
Infections
Infectious diseases
Male
Medicine and Health Sciences
Mortality
Multidrug resistance
Multidrug resistant organisms
Mutation
Mutation - genetics
Mycobacterium tuberculosis
Mycobacterium tuberculosis - classification
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - isolation & purification
Phylogeny
Polymorphism, Restriction Fragment Length
Public health
Resistance factors
Retrospective Studies
RNA polymerase
RpoB protein
Spoligotyping
Tuberculosis
Tuberculosis, Multidrug-Resistant - epidemiology
Tuberculosis, Multidrug-Resistant - genetics
title Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil
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