title: Multidrug resistant Mycobacterium tuberculosis: a retrospective katG and rpoB mutation profile analysis in isolates from a reference center in Brazil.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Flávia A D
authors.initials: FA
authors.lastname: de Freitas
authors.affiliation: Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vagner
authors.initials: V
authors.lastname: Bernardo
authors.affiliation: CNRS-Université Paris-Sud, Institut de Génétique et Microbiologie- Infection Genetics Emerging Pathogens Evolution Team, Orsay, France.
authors.forename: Michel K
authors.initials: MK
authors.lastname: Gomgnimbou
authors.affiliation: CNRS-Université Paris-Sud, Institut de Génétique et Microbiologie- Infection Genetics Emerging Pathogens Evolution Team, Orsay, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Sola
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Hélio R
authors.initials: HR
authors.lastname: Siqueira
authors.affiliation: Centro de Referência Professor Hélio Fraga, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Márcia A S
authors.initials: MA
authors.lastname: Pereira
authors.affiliation: Centro de Referência Professor Hélio Fraga, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Fátima C O
authors.initials: FC
authors.lastname: Fandinho
authors.affiliation: Laboratório de Biologia Molecular Aplicada a Micobacteria, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Harrison M
authors.initials: HM
authors.lastname: Gomes
authors.affiliation: Laboratório de Biologia Molecular Aplicada a Micobacteria, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Marcelo E I
authors.initials: ME
authors.lastname: Araújo
authors.affiliation: Laboratório de Biologia Molecular Aplicada a Micobacteria, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Suffys
authors.affiliation: Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Marques
authors.affiliation: Departamento de Bioquímica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Rodolpho M
authors.initials: RM
authors.lastname: Albano
mesh_terms: D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics*; D015373:Bacterial Typing Techniques; D001938:Brazil / Q000453:epidemiology; D002374:Catalase / Q000235:genetics*; D016000:Cluster Analysis; D012321:DNA-Directed RNA Polymerases; D003710:Demography; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009154:Mutation / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D012189:Retrospective Studies; D018088:Tuberculosis, Multidrug-Resistant / Q000453:epidemiology / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C505805:rpoB protein, Mycobacterium tuberculosis; D002374:Catalase; C480353:katG protein, Mycobacterium tuberculosis; D012321:DNA-Directed RNA Polymerases
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