Nanotherapy for controlling transmission and systemic infection by Candida auris: in vitro and in vivo studies

• Grant number: 24/07461-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Carlos Pelleschi Taborda
• Grantee: Gabriel Davi Marena
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

Candida auris is an emerging species of great clinical concern due to its multidrug-resistant capacity. C. auris is an opportunistic microorganism, responsible for causing systemic infection in immunocompromised and hospitalized patients. Its therapy is limited, which is a cause for concern since it is a species with a high capacity to acquire resistance to all classes of antifungals. The main factor responsible for the increase in cases is the high transmission among asymptomatic people due to the colonization of C. auris on skin or surfaces. In view of this, it is extremely important to investigate and develop new alternatives to control the transmission of this pathogen as well as develop new therapies for already infected patients. To this end, nanotechnology stands out with nanoscale systems that can contribute to better bioavailability, selectivity and better therapeutic activity and transmission control. Therefore, this work aims to develop and characterize nanomaterials to combat the colonization of C. auris as well as to control systemic infection. For activity against colonization, nanoemulsions loaded with non-glycosylated antibodies Anti-adhesin agglutinin-like sequence (ALS3) Human Recombinant (AntI-ALS3) will be developed using "Phage display" technology (NE@Anti-ALS3) for topical treatment. Subsequently, the anti-adhesion potential will be evaluated in cultures that mimic artificial skin. For therapy against systemic infection, adhesin/invasin Als3 presented by MHC class II of dendritic cells will be researched and synthesized. Chitosan nanoparticles (Nq) containing Als3 (Nq@Als3) will be developed and characterized by evaluating the size, polydispersity index, zeta potential and stability test using the dynamic light scattering (DLS) technique. Furthermore, transmission electron microscopy (TEM) and association efficiency and in vitro release assay will be performed. The safety profile of the nanoparticles will be evaluated against murine macrophages J774.16 (cytotoxicity) and in vivo model using Galleria mellonella (acute toxicity). The virulent potential of the strains used will be evaluated in a G. mellonella model. Finally, the antifungal and protective profile of the nanovaccine will be evaluated in in vivo models with G. mellonella and vaccinated and infected mice. Both nanotherapies are expected to present important physical characteristics of a nanoscale system and help control colonization, reducing transmission as well as improving the immunological response in in vivo models, contributing to the control of infection caused by C. auris.