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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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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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0104100</identifier><identifier>PMID: 25093512</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e104100-e104100</ispartof><rights>2014 de Freitas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 de Freitas et al 2014 de Freitas et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-5361778a6238d09d132937891c176e6960d82dd84802e9e4dd531e044b6344493</citedby><cites>FETCH-LOGICAL-c526t-5361778a6238d09d132937891c176e6960d82dd84802e9e4dd531e044b6344493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122415/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4122415/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25093512$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tyagi, Anil Kumar</contributor><creatorcontrib>de Freitas, Flávia A D</creatorcontrib><creatorcontrib>Bernardo, Vagner</creatorcontrib><creatorcontrib>Gomgnimbou, Michel K</creatorcontrib><creatorcontrib>Sola, Christophe</creatorcontrib><creatorcontrib>Siqueira, Hélio R</creatorcontrib><creatorcontrib>Pereira, Márcia A S</creatorcontrib><creatorcontrib>Fandinho, Fátima C O</creatorcontrib><creatorcontrib>Gomes, Harrison M</creatorcontrib><creatorcontrib>Araújo, Marcelo E I</creatorcontrib><creatorcontrib>Suffys, Philip N</creatorcontrib><creatorcontrib>Marques, Elizabeth A</creatorcontrib><creatorcontrib>Albano, Rodolpho M</creatorcontrib><title>Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Adult</subject><subject>Antimicrobial agents</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Typing Techniques</subject><subject>Biology and life sciences</subject><subject>Brazil - epidemiology</subject><subject>Catalase - genetics</subject><subject>Chemotherapy</subject><subject>Cluster Analysis</subject><subject>Demography</subject><subject>DNA-Directed RNA Polymerases</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple, Bacterial - genetics</subject><subject>Enzymes</subject><subject>Epidemics</subject><subject>Female</subject><subject>Genes</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Incidence</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Mortality</subject><subject>Multidrug resistance</subject><subject>Multidrug resistant organisms</subject><subject>Mutation</subject><subject>Mutation - 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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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