Contribution of the penicillin-binding proteins (PBPs) to beta-lactam resistance in Acinetobacter baumannii strains isolated from different Brazilian Regions

• Grant number: 12/15459-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2012
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Ana Cristina Gales
• Grantee: Rodrigo Cayô da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Carbapenems remain the main therapeutic option for treatment of Acinetobacter baumannii infections. Unfortunately, carbapenenem-resistant A. baumannii have emerged worldwide. Control of outbreaks caused by carbapenem-resistant A. baumannii is rarely achieved due to pathogen´s intrinsic characteristics. Among A. baumannii isolates, the production of ²-lactamase constitutes the most frequent mechanism of carbapenem resistance studied. Carbapenem-hydrolyzing enzymes belonging to the oxacilinase group are the most frequent enzymes reported. However, most of these enzymes poorly hydrolyze carbapenems. These findings strongly suggest that other mechanisms of beta-lactam resistance could be contributing to this phenotype. The penicillin-binding proteins (PBPs) have a vital role for the bacterial cell and therefore constitute the target for many of the antimicrobials clinically prescribed, including the ²-lactams. Recent studies have hypothesized that these proteins have a complex and important role in both pathogenesis and resistance of A. baumannii strains. Thus, the present study was designed to assess the contribution of PBPs in carbapenem-resistant A. baumannii strains isolated from different Brazilian regions. Would alterations in the PBPs be an additional mechanism to justify the high levels of carbapenem resistance found in OXA-23-producing A. baumannii isolated from Brazilian hospitals? Would less potent carbapenemases lead to PBP reorganization in A. baumannii? Would the selective pressure exerted by ²-lactams over A. baumannii PBPs be insignificant, since other resistance mechanisms would act at an earlier stage of peptideoglican biosynthesis? We hope with this study to answer these questions and, in this manner, to contribute to the understanding of this complex network of beta-lactam resistance in A. baumannii isolated from Brazilian hospitals.

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)

CARDOSO, JULIANA PROVASI; CAYO, RODRIGO; GIRARDELLO, RAQUEL; GALES, ANA CRISTINA. Diversity of mechanisms conferring resistance to beta-lactams among OXA-23-producing Acinetobacter baumannii clones. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 85, n. 1, p. 90-97, MAY 2016. (12/15459-6)

SILVA, KESIA ESTHER; CAYO, RODRIGO; CARVALHAES, CECILIA GODOY; CORREIA SACCHI, FLAVIA PATUSSI; RODRIGUES-COSTA, FERNANDA; RAMOS DA SILVA, ANA CAROLINA; CRODA, JULIO; GALES, ANA CRISTINA; SIMIONATTO, SIMONE. Coproduction of KPC-2 and IMP-10 in Carbapenem- Resistant Serratia marcescens Isolates from an Outbreak in a Brazilian Teaching Hospital. Journal of Clinical Microbiology, v. 53, n. 7, p. 2324-2328, JUL 2015. (12/15459-6)

GIRARDELLO, RAQUEL; VISCONDE, MARINA; CAYO, RODRIGO; BRESSAN QUEIROZ DE FIGUEIREDO, REGINA CELIA; DA SILVA MORI, MARCELO ALVES; LINCOPAN, NILTON; GALES, ANA CRISTINA. Diversity of polymyxin resistance mechanisms among Acinetobacter baumannii clinical isolates. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 87, n. 1, p. 37-44, JAN 2017. (10/12891-9, 12/15458-0, 12/15459-6)