Avaliação da formação de células persistentes em Acinetobacter baumannii

• Autor(a) principal: Barth Junior, Valdir Cristóvão
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
• Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/5488
• topic: BIOLOGIA MOLECULAR; BIOLOGIA CELULAR; AGENTES ANTIBACTERIANOS; ESTRESSE OXIDATIVO; CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL

Persistence is an antimicrobial tolerance phenotype with an unclear molecular background. Such tolerant cells (called persisters) correspond to small portions of the bacterial population and are capable of surviving excessive concentrations of the drug, even though they do not possess any specific resistance mechanism. The clinical impact of persisters lies on their capacity to resume multiplication and reestablish the infection after the concentration of the drug diminishes in the infection site, possibly being responsible for the re-incidence and for the chronic aspect of certain infectious diseases. This survival phenotype has been observed in several species; however reports involving A. baumannii are scarce. Therefore, this work aimed to evaluate the persistence phenotype to antimicrobial drugs in nosocomial isolates of A. baumannii, as well as verifying the possible contribution of the sodB gene, which is involved in the control of oxidative stress, and the pmrC gene, a determinant of polymyxins resistance, in persister cells formed upon polymyxin B exposure. In order to do so, clinical isolates of A. baumannii were exposed to high concentration of tobramycin and polymyxin B for 6 h and the number of surviving cells were estimated every 1.5 h. In addition, the gene expressions at transcription level of two isolates were evaluated after the exposure to polymyxin B for 5 h. A high heterogeneity in the ability to form persister cells was observed among the isolates, presenting no correlation between the fractions of persisters after tobramycin and polymyxin B treatments. These data may indicate genetic or epigenetic variations that are determinant to the development of this characteristic, and that are not related among drugs of different classes. Moreover, the preliminary results of the gene expression assays may suggest that the mechanism involved in the polymyxin B resistance phenotype does not directly participate in persistence to polymyxin B, nor indicate the participation of sodB in this phenotype. In conclusion, the molecular mechanisms for persistence are still to be determined, and this characterization is highly important to assist in the development of new therapeutic options.