Identification of new antibacterial agents in libraries of natural products

• Grant number: 15/19906-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2016
• End date: February 29, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Biochemistry of Microorganisms
• Principal Investigator: Andrea Dessen de Souza e Silva
• Grantee: Fernanda Rodrigues da Costa
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 17/12436-9 - ANTIBIO-BAC: exploring the bacterial cell wall as a target for novel antibiotherapies, AP.SPEC
• Associated scholarship(s): 18/07148-7 - New antibiotic development through exploration of the bacterial cell wall formation machinery, BE.EP.DR

Abstract

ABSTRACT Introduction: Antimicrobial resistance is a serious public health problem. Infections caused by bacteria that are resistant to several classes of antimicrobials are an increasingly common fact in the nosocomial environment. Once the therapeutic options have become inactive due to resistance issues, hospital therapies can be limited to antimicrobials that are often more toxic and less effective. Thus, this study aims at screening libraries of novel natural products containing a high percentage of biodiversity samples from Brazil and Antarctica, which available at the Laboratório Nacional de Biociências (LNBio- CNPEM) against a Gram-negative and a Gram-positive bacterial cell line in order to identify new compounds inhibit or totally block bacterial growth. Justification: Pathogenic bacteria suffer an intense selective pressure caused by the constant use of antibiotics and antiseptic compounds, resulting in the spread of resistance markers in the hospital environment, and consequently multidrug resistance. Unfortunately it happens faster than the introduction of new antimicrobial agents in clinics. For this reason, the landscape of antimicrobial resistance worldwide is threatening, especially in Latin America which accounts for a wide range of pathogens displaying different resistance mechanisms. This fact, combined with the low perspective of introduction of new therapeutic options by pharmaceutical companies, underlines the importance of undertaking studies aimed at discovering novel compounds with antibiotic action. This research project is one of the first efforts to identify potential new antibiotics from natural product libraries of the Brazilian biodiversity. Materials and Methods: Initially, we will screen four different types of natural product libraries which are available in the Chemical Laboratory of Natural Products (LQPN-LNBio), with the purpose of identifying novel compounds with antibiotic action. We will employ two non-pathogenic laboratory strains (Escherichia coli K12 and Streptococcus pneumoniae R6). The initial tests will be made on solid and liquid bacterial growth media, and the best method will be chosen for the library screening steps (which represents approximately 10,000 compounds). The most promising compounds that are able to inhibit or completely prevent the growth of such strains will be characterized. We will determine the minimum inhibitory concentration (MICs) for each compound using laboratory and pathogenic strains, the latter in collaboration with the laboratory of Professor Bernard Joris at the University of Liege in Belgium. Since the libraries contain both extracts and purified compounds, if our 'hits' are extract samples we will perform their re-fragmentation in collaboration with the group of Dr. Daniela Trivella, in order to identify active substances. One major, and exciting, challenge in the project will be to identify the biochemical pathway that is inhibited/affected by our hits. The scientific and technological environment of the LNBio is optimal for the development of this challenging and novel project. (AU)

Scientific publications

(4)

(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)

STALOCH, BRENDON EGON KORMANN; NIERO, HENRIQUE; DE FREITAS, ROBERT CARDOSO; BALLONE, PATRICIA; RODRIGUES-COSTA, FERNANDA; TRIVELLA, DANIELA BARRETTO BARBOSA; DESSEN, ANDREA; DA SILVA, MARCUS ADONAI CASTRO; LIMA, ANDRE OLIVEIRA DE SOUZA. Draft genome sequence of Psychrobacter nivimaris LAMA 639 and its biotechnological potential. DATA IN BRIEF, v. 41, p. 11-pg., 2022-04-01. (14/10753-9, 17/12436-9, 15/19906-5)

DE FELICIO, RAFAEL; BALLONE, PATRICIA; BAZZANO, CRISTINA FREITAS; ALVES, LUIZ F. G.; SIGRIST, RENATA; INFANTE, GINA POLO; NIERO, HENRIQUE; RODRIGUES-COSTA, FERNANDA; FERNANDES, ARTHUR ZANETTI NUNES; TONON, LUCIANE A. C.; et al. Chemical Elicitors Induce Rare Bioactive Secondary Metabolites in Deep-Sea Bacteria under Laboratory Conditions. METABOLITES, v. 11, n. 2, FEB 2021. (14/10753-9, 17/12436-9, 15/19906-5)

RODRIGUES-COSTA, FERNANDA; SLIVINSKI, JULIANO; IOCA, LAURA P.; BERTONHA, ARIANE F.; DE FELICIO, RAFAEL; DA CUNHA, MARCOS GUILHERME; DA MATA MADEIRA, PAULO VINICIUS; CAUZ, ANA C. G.; TRINDADE, DANIEL MARAGNO; FREIRE, VITOR F.; et al. Merulinic acid C overcomes gentamicin resistance in Enterococcus faecium. BIOORGANIC CHEMISTRY, v. 100, JUL 2020. (16/05133-7, 13/50228-8, 11/52067-6, 17/12436-9, 15/19906-5, 14/11980-9)

MARTINS, ALEXANDRE; CONTRERAS-MARTEL, CARLOS; JANET-MAITRE, MANON; MIYACHIRO, MAYARA M.; ESTROZI, LEANDRO F.; TRINDADE, DANIEL MARAGNO; MALOSPIRITO, CAIQUE C.; RODRIGUES-COSTA, FERNANDA; IMBERT, LIONEL; JOB, VIVIANA; et al. Self-association of MreC as a regulatory signal in bacterial cell wall elongation. NATURE COMMUNICATIONS, v. 12, n. 1, MAY 20 2021. (17/12436-9, 15/19906-5, 11/52067-6, 18/07148-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, Fernanda Rodrigues da. Identification of new antibacterial agents in libraries of natural products. 2020. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.