# Endothelial invasion by yeast-phase Candida

> **NIH NIH R01** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2020 · $547,575

## Abstract

Project Summary/Abstract
Hematogenously disseminated candidiasis is a major problem in hospitalized patients.
Candida species are the third most commonly isolated organism from the bloodstream of
these patients, and the attributable mortality of candidemia is 20% to 38%, despite
currently available therapy. Candida albicans now causes less than 50% of cases of
disseminated candidiasis, whereas the incidence of invasive infections caused by
Candida glabrata is steadily increasing. The majority of C. glabrata isolates are
fluconazole-resistant and a rising percentage are echinocandin-resistant. Therefore, new
methods to prevent and treat disseminated candidiasis are urgently needed. During
hematogenously disseminated candidiasis, blood-borne organisms must invade the
endothelial cell lining of the vasculature to reach the target organs. Recently, we
discovered that heat-labile serum proteins bind to the surface of yeast-phase C. albicans,
C. glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei (collectively
called Yeast-Phase Candida; YPC). Acting as bridging molecules, these serum proteins
interact with receptors on the endothelial cell surface and induce endocytosis of the yeast.
Based on these novel data, we hypothesize that the capacity of YPC to invade the
endothelial cell lining of the vasculature is critical for the organism to escape from the
bloodstream and establish a deep-seated infection. Our goal is to determine which
endothelial cell receptors mediate the endocytosis of YPC, identify the serum proteins that
act as bridging molecules and induce endocytosis, and define the fungal gene products
that mediate binding to serum bridging molecules and serum-induced endocytosis. The
experiments described in this proposal will identify and characterize a previously
unexplored aspect of the host-pathogen interaction that plays a vital role in
hematogenously disseminated infection by most medically important species of Candida.
Utilizing this body of research, our ultimate goal is to develop new therapeutic strategies
to block the escape of Candida spp. from the bloodstream. The use of bridging molecules
to induce endothelial cell endocytosis is one of the first pathogenic mechanisms to be
identified that is common to multiple species of Candida. Thus, interventions that inhibit
this process hold promise to have broad therapeutic applicability.

## Key facts

- **NIH application ID:** 9932335
- **Project number:** 5R01AI124566-05
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** Scott G Filler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $547,575
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932335

## Citation

> US National Institutes of Health, RePORTER application 9932335, Endothelial invasion by yeast-phase Candida (5R01AI124566-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932335. Licensed CC0.

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