Innovative approaches for preventing Candidozyma auris adhesion: Targeting SCF1 with monoclonal antibodies

• Grant number: 25/00673-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Arnaldo Lopes Colombo
• Grantee: Felipe de Camargo Ribeiro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 21/10599-3 - The Antimicrobial Resistance Institute of São Paulo (The Aries Project), AP.CEPID

Abstract

Candidozyma auris is an emerging yeast species with significant public health impact due to its ability to cause outbreaks of invasive infections and its potential to develop multidrug resistance to antifungal treatments. Cdz. auris is not part of the native microbiota of the population; it is an opportunistic microorganism associated with invasive infections in patients with degenerative and neoplastic diseases who are hospitalized in intensive care units, where they are exposed to invasive medical procedures and selective pressure from antimicrobials. The main factor responsible for the rise in invasive infections caused by Cdz. auris is its high transmission among asymptomatic individuals due to its colonization on skin or hospital surfaces. Therefore, the primary objective of this project is to develop and characterize monoclonal antibodies that antagonize the Surface Colonization Factor (SCF1) of Cdz. auris and evaluate their anti-adhesive action in an infection model using 3D reconstructed epithelial tissue. Initially, an in silico analysis will be conducted to identify epitopes with immunogenic, antigenic, and non-toxic properties capable of inducing the production of IFN-gamma and that are conserved across different yeast isolates. After the in silico analysis, the promising epitopes will be selected for the production of recombinant anti-SCF1 antibodies using the Phage display technology. Once the antibodies are obtained, the anti-adhesive potential of the recombinant antibodies will be assessed in a reconstituted human epidermis model using isolates from clades I (South Asian), III (South African), and IV (South American), as well as control strains (C. auris CBS 10913 and C. albicans SC 5314). After 4 and 24 hours, colony-forming units (CFUs) will be quantified to evaluate the influence of the treatment on adhesion and biofilm formation in the reconstituted human epidermis model. Finally, these samples will also undergo histological analysis for microscopic visualization of yeast and epidermal structures under different treatment conditions. This set of methods aims to develop an effective strategy against the colonization of Cdz. auris, an emerging yeast with high resistance to conventional treatments.