Caracterização da resistência a quinolonas em Mycobacterium abscessus subsp. bolletii e outras micobactérias de crescimento rápido relacionadas

• Ano de defesa: 2011
• Autor(a) principal: Moura, Vinicius Calado Nogueira de
• Orientador(a): Duarte, Rafael Silva
• Banca de defesa: Guaraldi, Ana Luiza de Mattos , Oelemann, Walter Martin Roland , Fonseca, Leila de Souza
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Microbiologia
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: Micobactérias de crescimento rápido (MCR); Regiões determinantes da resistência a quinolonas (RDRQ); Genes gyrA e gyrB; Micobactérias; Quinolonas; Infecções por Mycobacterium
• Palavras-chave em Inglês: Rapidly growing mycobacteria (RGM); Quinolone resistance determining regions (QRDR); gyrA and gyrB genes.
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::MICROBIOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/14411

Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) have been reported in many Brazilian states since 2000. Most of the cases were mainly associated to Mycobacterium massiliense, recently renamed as Mycobacterium abscessus subsp. bolletii, BRA100 clone recovered from patients who had undergone invasive procedures, in which medical instruments have not been properly sterilized and / or disinfected. Since quinolones have represented an option for the treatment of general RGM infections and suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro activities of four generations of quinolones for clinical and reference RGM by broth microdilution, and analysis of peptide sequences of the quinolone resistance determining regions (QRDR) of GyrA and GyrB after DNA sequencing followed by amino acid translation. Fifty four isolates of M. abscessus subsp bolletii, including clone BRA100, recovered in different states of Brazil, and 19 reference strains of RGM species were characterized. All 54 M. abscessus subsp. bolletii isolates were resistant to all generations of quinolones and showed the same amino acids in the QRDR including the Ala-83 in GyrA, Arg-447 and Asp-464 in GyrB, described as responsible for an intrinsic low level of resistance to quinolones in mycobacteria. But other RGM species presented distinct susceptibilities to this class of antimicrobials and patterns of mutations contrary to what has been traditionally defined, suggesting that other mechanisms of resistance, different from gyrA or gyrB mutations, may also be involved in resistance to high levels of quinolones.