New scientific approach against antimicrobial resistance using terpene-coupled nanotubes

• Grant number: 17/01206-2
• Support Opportunities: Scholarships abroad - Research
• Effective date (Start): March 01, 2018
• Effective date (End): July 31, 2018
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Rodney Alexandre Ferreira Rodrigues
• Grantee: Rodney Alexandre Ferreira Rodrigues
• Host Investigator: Garry Laverty
• Host Institution: Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA). Universidade Estadual de Campinas (UNICAMP). Paulínia , SP, Brazil
• Research place: Queen's University Belfast, Northern Ireland

Abstract

The effectiveness of antibiotics has been falling since they were introduce into modern medicine at least 70 years ago. The increasing and alarming rate of antimicrobial resistance particularly related to G (-) infections have challenge researchers in discovery new antibacterial compounds. Some publications describe the use of a particular class of antimicrobial agents based on the self-assembling peptides nanotubes (PNT) formed by stacking cyclic peptides. Cyclic PNT hold great promise as drug delivery carriers but have never been explore for this purpose. The intention of this project is to apply commercial peptides made by short cyclic D, L-peptides attached with terpenes from essential oils. The peptides and the terpenes aimed to act synergistically as drug delivery systems being a selective target to the outer membrane of G (-) bacteria extending the spectrum of activity for G(+) antibiotics that are not active against G(-). The choice of essential oil will done according to previous publication of collaborators at CPQBA/UNICAMP (Duarte et al., 2007; Duarte et al., 2005; Duarte et al., 2004; Sartoratto et al., 2004). These peptides will target and neutralize associated outer membrane lipopolysaccharides (LPS) due to their architecture similarity to polymycin. PNTs will display increased selectivity toward the G (-) pathogens such as Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae compared to G (+) isolates. PNTs will tested by in vitro biostability assay. This project proposes a new approach to form a bioconjugated based on the adsorption/inclusion of terpenes in peptides nanotubes aiming to enrich the antimicrobial activity to those nanotubes on LPS in G (-) bacterial outer membranes. The proposed methodology is similar to the one applied to pharmaceuticals based on cyclodextrins inclusion of molecules but with none similarity to microencapsulation to produce microparticles/capsules. It is worth remembering that there are no reports in the literature of the absorption of terpenes in nanotubes produced with peptides, therefore it is an unpublished work. (AU)