Assessment of virulence characteristics of cells dispersed from biofilms formed by clinical isolates of Candida albicans responsible for persistent candidemia

• Grant number: 22/01975-4
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): September 01, 2022
• Effective date (End): December 31, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Arnaldo Lopes Colombo
• Grantee: Felipe de Camargo Ribeiro
• Supervisor: Priya Uppuluri
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: Harbor-UCLA Medical Center, United States
• Associated to the scholarship: 21/00527-5 - Mechanisms of virulence and pathogenicity expressed by strains of Candida spp. during episodes of persistent Candidemia, BP.PD

Abstract

Although candidemia is a concern worldwide, the incidence and mortality rates are particularly staggering in Brazil. According to several authors, for every 1,000 hospital admission in tertiary care Brazilian hospitals, up to 6 patients will develop candidemia and half of them will die from this infection during their hospital admission. Clearly, the management of invasive candidiasis is suboptimal in our medical centers and new strategies for preventing and controlling candidemia deserve investigation. In this scenario, our main proposal is to better characterize attributes of virulence of C. albicans related to episodes of persistent fungemia documented in susceptible hosts submitted to antifungal therapy. The pathogenicity of C. albicans involves a complex and co-regulated cell signalization pathways responsible for biofilm formation, fungal filamentation, production of proteolytic enzymes, and cells dispersion. In contrast with the large number of studies addressing the impact of biofilm production in antifungal resistance and Candida pathogenesis, there is a lack of data related to the biologic behavior and virulence aspects of yeast cells dispersed from mature biofilms. Our main interest is to characterize virulence factors of C. albicans isolates cultured from patients with persistent candidemia. We hypothesize that Candida isolates able to evade immunologic response of the host along 3 days of antifungal therapy (isolates from episodes of persistent candidemia) will be able to produce mature biofilms with dispersed cells exhibiting a significantly higher capacity to adhere to endothelial cells, invade host tissues, and cause invasive disease, when compared to Candida isolates recovered from the first day of infection. A total of 30 C. albicans isolates from patients with candidemia will be used in this study. The isolates were divided into three groups: Group I: 10 isolates from patients who had a single episode of candidemia, with negative subsequent cultures; Group II: 10 isolates from the first day of infection of patients who developed persistent candidemia (baseline cultures); Group III: 10 isolates obtained after 72h of antifungal therapy (persistent candidemia cultures). Biofilms under a continuous flow of fresh medium will be developed to produce populations of dispersed cells of C. albicans isolates of all Groups mentioned above (I, II, and III) and will be compared in relation to: capacity to produce biofilm and dispersed cells, quantification of chitin and glucan, proteinase and hemolytic activity, endothelial cell adhesion and damage, modulation of a specific set of virulence gene expression and C. elegans killing assay. (AU)