Characterization of antimicrobial resistance genes in KPC-producing Klebsiella pneumoniae isolated from hospitals of São Paulo State, Brazil

• Grant number: 14/23715-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): August 01, 2015
• Effective date (End): July 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Doroti de Oliveira Garcia
• Grantee: Maria Fernanda Campagnari Bueno
• Host Institution: Instituto Adolfo Lutz (IAL). Coordenadoria de Controle de Doenças (CCD). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Klebsiella pneumoniae producing extended spectrum beta-lactamases(ESBL) and KPC are often involved in health care associated infections (HAI). Plasmids responsible for producing these enzymes may carry genes responsable for resistance to aminoglycosides. Recently, a new mechanism for resistance to aminoglycosides was detected in Gram-negative bacteria, 16S rRNA methyltransferases, which confer high-level resistance to these antimicrobial agents. In Brazil, in 2007, it was reported the 16S rRNA methyltransferase RmtD in P. aeruginosa strains which coproduced the metallo-²-lactamase SPM-1. Recently, a new methyltransferase named RmtG was described in K. pneumoniae, in São Paulo state, with approximately 57% similarity with the RmtD. Genes encoding RmtD and RmtG are located on plasmids and can easily disseminate to other species. A major concern is the emergence of multi-resistant strains producing 16S rRNA methyltransferases through the accumulation of several other antimicrobial resistance genes. Aminoglycosides are important for the treatment of serious infections caused by enterobacteria and the production of 16S rRNA methyltransferases, associated with the production of beta-lactamase, could limited treatment options. The aim of this study is to determine the complete sequence of plasmids carring rmtD1, rmtD2 and rmtG genes in Klebsiella pneumoniae isolated in hospitals of São Paulo state. Three strains of K. pneumoniae previously characterized as producers of one methylases RmtD1, RmtD2 and RmtG will be submitted to transformation experiments and plasmid extraction. Then, it will be held the complete sequencing of the plasmids by Illumina platform and PacBio RS II real-time single-molecule. Analysis of full plasmids sequences that carry these 16S rRNA methyltransferases will be important to determine the location and the genetic enviroment of these methyltransferases genes and if different genes can be carried on the same plasmid. Furthermore, it will be possible for us to understand the acquisition of various antimicrobial resistance genes, as well as the facility of transmission of these plasmids to other bacteria. (AU)

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)

BUENO, MARIA FERNANDA C.; FRANCISCO, GABRIELA R.; GARCIA, DOROTI DE OLIVEIRA; DOI, YOHEI. Complete Sequences of Multidrug Resistance Plasmids Bearing rmtD1 and rmtD2 16S rRNA Methyltransferase Genes. Antimicrobial Agents and Chemotherapy, v. 60, n. 3, p. 1928-1931, MAR 2016. (12/21709-5, 14/23715-8)