Production of human recombinant Peptidoglycan recognition protein (rPGLYRP3) and antimicrobial peptide (AMP-rPGLYRP3) in Pichia pastoris and analysis of antibacterial activity in opportunistic strains

• Grant number: 21/00425-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2021
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Maria Cristina da Silva Pranchevicius
• Grantee: Pedro Mendes Laprega
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Over the last few years, deaths caused by multidrug-resistant bacteria (MDRB) have been rising at an alarming rate, therefore, the search for new compounds capable of dealing with these microorganisms is highly important. Amongst the compounds with potential for new therapies, there are the peptidoglycan recognition proteins (PGLYRPs) and antimicrobial peptides (AMPs). PGLYRPs recognize conserved molecular patterns in infectious organisms and unleash innate immune responses, including phagocytosis, antimicrobial and pro-inflammatory genes expression and cytokines production. AMPs, including those deriving from host protein fragments, are multifunctional, being capable of mediating many anti-bacterial and immunomodulatory functions and stimulating angiogenesis. Considering the search for new solutions for the emerging MDRB problem, in this study we are proposing the heterologous expression of not only PGLYRP3, but also of an antimicrobial peptide (AMP-rPGLYRP3) (PVMPRKVCPNIIKRS) within this encoded protein, already identified by us, in a Pichia pastoris system. In addition, we intend to analyze the antimicrobial activity of both rPGLYRP3 and AMP-rPGLYRP3 on opportunistic bacteria. In silico analysis regarding the peptide AMP-PGLYRP3, also performed by us, shows that it is a possible non-toxic and non-allergenic anti-bacterial candidate, being, most likely, not active against human erythrocytes, while active against the bacteria species Klebsiella pneumoniae. Therefore, the results from this project may amplify our knowledge regarding the anti-bacterial activity of both PGLYRP3 and AMP-rPGLYRP3, assisting, in the future, the development of new medications and, consequently, control bacterial infections.

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)

RODRIGUES, SAULO HENRIQUE; NUNES, GUSTAVO DANTAS; SOARES, GABRIELA GUERRERA; FERREIRA, ROUMAYNE LOPES; DAMAS, MARCELO SILVA FOLHAS; LAPREGA, PEDRO MENDES; SHILLING, REBECCA ELIZABETH; CAMPOS, LESLIE CAMELO; DA COSTA, ANDREA SOARES; MALAVAZI, IRAN; et al. First report of coexistence of blaKPC-2 and blaNDM-1 in carbapenem-resistant clinical isolates of Klebsiella aerogenes in Brazil. FRONTIERS IN MICROBIOLOGY, v. 15, p. 21-pg., 2024-02-14. (21/00425-8, 22/16872-6, 18/20697-0, 21/08423-4, 22/01223-2, 18/24213-7, 23/08917-2, 20/11964-4, 22/12429-0)

DAMAS, MARCELO SILVA FOLHAS; FERREIRA, ROUMAYNE LOPES; CAMPANINI, EMELINE BONI; SOARES, GABRIELA GUERRERA; CAMPOS, LESLIE CAMELO; LAPREGA, PEDRO MENDES; DA COSTA, ANDREA SOARES; FREIRE, CAIO CESAR DE MELO; PITONDO-SILVA, ANDRE; CERDEIRA, LOUISE TEIXEIRA; et al. Whole genome sequencing of the multidrug-resistant Chryseobacterium indologenes isolated from a patient in Brazil. FRONTIERS IN MEDICINE, v. 9, p. 20-pg., 2022-07-28. (18/24213-7, 21/08423-4, 20/11964-4, 18/20697-0, 21/00425-8)