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Study of the heterogeneous resistance to vancomycin in Staphylococcus aureus by comparative single-cell genomics of subpopulations in a single isolate

Grant number: 13/12107-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2016
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Elsa Masae Mamizuka
Grantee:John Anthony Mcculloch
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The first line of choice for the treatment of infections caused by Methicillin-Resistant Staphylococcus aureus is the antibiotic vancomycin. MRSA strains which do not respond to treatment with vancomycin can be characterized as being either resistant (VRSA) or intermediate (VISA). VISA strains present cell wall thickening as a result of a string of mutations in possibly different sets of genes, leading to vancomycin resistance. Furthermore, some strains present a heterogeneous mode of resistance (hVISA) in which sub-populations within a colony present a minimal inhibitory concentration (MIC) of vancomycin higher than that of the median and modal MIC of the entire population. These sub-populations with higher than median MICs of vancomycin may present mutations in genes which would not be detected by sequencing of DNA extracted from a cultured mass of cells because the majority wild-type polymorph would dominate the population. To circumvent this predicament, we propose to use a single-cell approach in order to identify which of the mutated genes attributed to the VISA phenotype are already found in all hVISA populations and which are present in only higher MIC subpopulations. Genomic DNA extracted from single hVISA cells isolated by laser microdissection will be amplified by MDA using phi29 DNA polymerase and sequenced using the SOLiD platform. The same will be carried out for VISA cells and vancomycin susceptible S. aureus (VSSA) cells. Alignment of all genome scaffolds obtained will permit the identification of coding sequence polymorphisms within hVISA populations and between VISA, hVISA and VSSA.

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Scientific publications (6)
(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)
BRASILIENSE, DANIELLE MURICI; BATISTA LIMA, KARLA VALERIA; PEREZ-CHAPARRO, PAULA JULIANA; MAMIZUKA, ELSA MASAE; SOUZA, CINTYA DE OLIVEIRA; GUIMARAES DUTRA, LIVIA MARIA; MCCULLOCH, JOHN ANTHONY. Emergence of carbapenem-resistant Acinetobacter pittii carrying the bla(OXA-72) gene in the Amazon region, Brazil. DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, v. 93, n. 1, p. 82-84, . (13/12107-4)
DE ALMEIDA, LARA M.; PIRES, CARLOS; CERDEIRA, LOUISE T.; DE OLIVEIRA, THEO G. M.; MCCULLOCH, JOHN ANTHONY; PEREZ-CHAPARRO, PAULA JULIANA; SACRAMENTO, ANDREY G.; BRITO, ARTEMIR C.; DA SILVA, JOAS L.; DE ARAUJO, MARIA RITA E.; et al. Complete Genome Sequence of Linezolid-Susceptible Staphylococcus haemolyticus Sh29/312/L2, a Clonal Derivative of a Linezolid-Resistant Clinical Strain. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 3, n. 3, . (12/16108-2, 13/06331-9, 12/20915-0, 13/12107-4)
MCCULLOCH, JOHN ANTHONY; DE OLIVEIRA SILVEIRA, ALESSANDRO CONRADO; LIMA MORAES, ALINE DA COSTA; PEREZ-CHAPARRO, PAULA JULIANA; SILVA, MANOELLA FERREIRA; ALMEIDA, LARA MENDES; D'AZEVEDO, PEDRO ALVES; MAMIZUKA, ELSA MASAE. Complete Genome Sequence of Staphylococcus aureus FCFHV36, a Methicillin-Resistant Strain Heterogeneously Resistant to Vancomycin. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 3, n. 4, . (12/20915-0, 13/12107-4)
PEREZ-CHAPARRO, PAULA JULIANA; MCCULLOCH, JOHN ANTHONY; MAMIZUKA, ELSA MASAE; LIMA MORAES, ALINE DA COSTA; FAVERI, MARCELO; FIGUEIREDO, LUCIENE CRISTINA; DUARTE, POLIANA MENDES; FERES, MAGDA. Do different probing depths exhibit striking differences in microbial profiles?. JOURNAL OF CLINICAL PERIODONTOLOGY, v. 45, n. 1, p. 26-37, . (13/23767-5, 12/20915-0, 13/12107-4)
FERNANDES, MIRIAM R.; MCCULLOCH, JOHN A.; VIANELLO, MARCO A.; MOURA, QUEZIA; PEREZ-CHAPARRO, PAULA J.; ESPOSITO, FERNANDA; SARTORI, LUCIANA; DROPA, MILENA; MATTE, MARIA H.; LIRA, DEBORA P. A.; et al. First Report of the Globally Disseminated IncX4 Plasmid Carrying the mcr-1 Gene in a Colistin-Resistant Escherichia coli Sequence Type 101 Isolate from a Human Infection in Brazil. Antimicrobial Agents and Chemotherapy, v. 60, n. 10, p. 6415-6417, . (13/12107-4)
PEREZ-CHAPARRO, PAULA JULIANA; CERDEIRA, LOUISE TEIXEIRA; QUEIROZ, MAISE GOMES; SILVA DE LIMA, CLAYTON PEREIRA; LEVY, CARLOS EMILIO; PAVEZ, MONICA; LINCOPAN, NILTON; GONCALVES, EVONNILDO COSTA; MAMIZUKA, ELSA MASAE; MELLO SAMPAIO, JORGE LUIZ; et al. Complete Nucleotide Sequences of Two bla(KPC-2)-Bearing IncN Plasmids Isolated from Sequence Type 442 Klebsiella pneumoniae Clinical Strains Four Years Apart. Antimicrobial Agents and Chemotherapy, v. 58, n. 5, p. 2958-2960, . (12/20915-0, 13/12107-4)

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