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Evaluation of the mechanisms of resistance to beta-lactams among Burkholderia cenocepacia clinical isolates recovered from bloodstream infections

Grant number: 14/12224-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2014
Effective date (End): May 22, 2016
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Ana Cristina Gales
Grantee:Lorena Cristina Corrêa Fehlberg
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Cystic fibrosis patients usually become colonized by Burkholderia cepacia complex species (Bcc) species. Part of these patients will become infected along their lifetime what has lead to higher mortality rates. The beta-lactams and trimethoprim/sulfamethoxazole are antimicrobials commonly prescribed for treatment of infections caused by Bcc. However, beta-lactam resistance has already emerged among Bcc isolates. This scenario gets more complicated because resistant bacteria usually carry additional resistant determinants. Among the mechanisms of beta-lactam resistance, beta-lactamase production is the most clinically important and studied mechanism. The contribution of other mechanism of resistance to beta-lactams like target site mutations is still unknown. The penicillin-binding-proteins (PBPs) exert a fundament role in the bacterial survival. For this reason, they constitute the target for many antimicrobials, including all beta-lactams. Beta-lactam antibiotics are steriochemical analogues of immature petideoglycan subunits, and covalently bind to the PBPs active serine site. Many studies performed with Pseudomonas aeruginosa have shown that hyperexpression of chromosomal AmpC is co-regulated by PBP-4 showing that mechanisms of beta-lactam resistance are more complex than it was initially thought. Based on this fact, would the production of PenA coupled with the PBP alteration be responsible for the ceftazidime resistance found among Bcc clinical isolates? The aim of this study is to elucidate the contribution of production of penicillinase Pen, the most important beta-lactamase in Burkholderia spp., and the PBPs alteration in conferring beta-lactam resistance among Bcc clinical isolates recovered from bloodstream infections of patients admitted to a Brazilian Teaching Hospital in the last ten years. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MARTINS, WILLAMES M. B. S.; NARCISO, ANA CLARA; CAYO, RODRIGO; SANTOS, STEFANIE VANESSA; FEHLBERG, LORENA C. C.; RAMOS, PATRICIA LOCOSQUE; DA CRUZ, JOAO BATISTA; GALES, ANA CRISTINA. SPM-1-producing Pseudomonas aeruginosa ST277 clone recovered from microbiota of migratory birds. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 90, n. 3, p. 221-227, . (14/12224-3, 17/02258-6)
CORDEIRO-MOURA, JHONATHA RODRIGO; CORREA FEHLBERG, LORENA CRISTINA; NODARI, CAROLINA SILVA; DE MATOS, ADRIANA PEREIRA; ALVES, VINICIUS DE OLIVEIRA; CAYO, RODRIGO; GALES, ANA CRISTINA. Performance of distinct phenotypic methods for carbapenemase detection: The influence of culture media. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 96, n. 1, . (14/12224-3)

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