Mechanisms of antibiotic resistance aquisition by bacteria causing infection of human urinary tract: a farmacogenomic and biopharmaceutic design

• Grant number: 11/21685-6
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2012
• End date: January 31, 2014
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Marcelo Lancellotti
• Grantee: Marcelo Lancellotti
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The urinary tract infection (UTI) is a very common condition, characterized by the presence of microorganisms in the urinary system. These diseases are responsible for much of the infectious processes acquired in the community and hospital settings. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae are described in the literature as the main responsible for the causes of UTI. The indiscriminate use of antibiotics over time caused the pathogens create adaptive mechanisms of resistance to various existing drugs, making it the target of concern for public health agencies, especially when it comes to hospitals. The metabolism of commonly used antibiotics are not targets for pharmacogenomics studies of the processes of hepatic metabolism of the active forms of antibiotics to treat these infections. This work will evaluate the resistance profile of bacteria that cause UTI and correlate subefetivas release rates of different ²-lactam antibiotics and quinolones in the acquisition of resistance "in vitro" (with the use of nanocarrier such as micellar systems, for controlled release of drugs), using nanoformulações controlled release, and especially "in vivo" to check the profiles of the polymorphic gene responsible for the hepatic metabolism of the antibiotic class of beta-lactams and quinolones in patients with recurrent infections of the ITU. In the latter case, the profiles will be evaluated for screening of polymorphisms obtained by the method of High Resolution Melt - Real Time PCR - followed by sequencing of the gene containing the polymorphism of interest. The polymorphism of interest will be selected by the recurrence of infection with multidrug-resistant bacteria, in agreement with differences in the profile of nucleotide bases of the genes responsible for metabolism and release of ß-lactams and quinolones by genes of cytochrome P - CYP, especially CYP450. Moreover, the tests "in vivo" and "in vitro" controlled release, compared to bacterial cultures that could provide resistance to the acquisition of data for understanding the process of development of bacterial resistance to antibiotics in this study. (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)

ALVES, DANILO ANTONINI; MACHADO, DAISY; MELO, ADRIANA; CARNEIRO PEREIRA, RAFAELLA FABIANA; SEVERINO, PATRICIA; DE HOLLANDA, LUCIANA MARIA; ARAUJO, DANIELE RIBEIRO; LANCELLOTTI, MARCELO. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. BIOMED RESEARCH INTERNATIONAL, v. 2016, p. 10-pg., 2016-01-01. (11/21822-3, 11/21685-6, 14/14457-5)

ALVES, DANILO ANTONINI; MACHADO, DAISY; MELO, ADRIANA; CARNEIRO PEREIRA, RAFAELLA FABIANA; SEVERINO, PATRICIA; DE HOLLANDA, LUCIANA MARIA; ARAUJO, DANIELE RIBEIRO; LANCELLOTTI, MARCELO. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. BIOMED RESEARCH INTERNATIONAL, 2016. (11/21685-6, 14/14457-5, 11/21822-3)

VARELA, JULIA NOGUEIRA; KRAEHENBUEHL AMSTALDEN, MARIA CECILIA; CARNEIRO PEREIRA, RAFAELLA FABIANA; DE HOLLANDA, LUCIANA MARIA; CERAGIOLI, HELDER JOSE; BARANAUSKAS, VITOR; LANCELLOTTI, MARCELO. Haemophilus influenzae porine ompP2 gene transfer mediated by graphene oxide nanoparticles with effects on transformation process and virulence bacterial capacity. JOURNAL OF NANOBIOTECHNOLOGY, v. 12, APR 16 2014. (11/21685-6, 11/14079-2, 12/15046-3)