# Regulation of Protein Synthesis During the C. albicans-Macrophage Interaction

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $193,840

## Abstract

PROJECT SUMMARY/ABSTRACT
Candida albicans, the most commonly isolated human fungal pathogen, is responsible for a wide variety of
systemic and mucosal infections. Immunocompromised individuals, including cancer patients on
chemotherapy, AIDS patients, neonates, and organ transplant recipients, are particularly susceptible to
infection. A central feature of C. albicans pathogenesis is this organism’s ability to counteract host immune
defenses. In particular, C. albicans has evolved a variety of mechanisms to promote both survival in the
phagosome of host macrophages as well as macrophage killing. While previous whole-genome
transcriptional profiling experiments have provided important insights into these processes, very little is known
about translational changes in gene expression that are associated with the C. albicans-macrophage
interaction. Especially given that transcriptional analyses can often provide an imperfect proxy for monitoring
protein expression due to extensive regulation of protein synthesis, studying translational control of the C.
albicans-macrophage interaction is more likely to identify novel mechanisms required for C. albicans survival
and pathogenicity as well as translational regulatory events associated with currently known mechanisms,
that have not been previously characterized. Several lines of evidence suggest that translational mechanisms
play an important role in the ability of C. albicans to survive in the phagosome and eventually kill host
macrophages, including the observation that C. albicans proteins involved in a variety of processes critical for
survival, including the glyoxylate cycle, fatty acid oxidation and the response to oxidative stress are
expressed during the early stage of macrophage internalization, despite a widespread down-regulation of
protein synthesis. Previous work from our laboratory has also shown that a key regulator of the C. albicans
yeast-filament transition, important for macrophage lysis, is controlled by a 5’ UTR-mediated translational
efficiency mechanism and results from an RNA-seq analysis suggest that several C. albicans genes involved
in processes important for macrophage survival and lysis could be controlled by a similar mechanism. Our
hypothesis is that translational efficiency mechanisms play an important role in controlling C. albicans survival
in the phagosome as well as macrophage killing. In order to address this hypothesis we will first, using whole-
genome ribosome profiling, determine both host and pathogen global translational profiles associated with the
C. albicans-macrophage interaction. Second, we will characterize selected translational mechanisms
specifically important for C. albicans macrophage survival and killing. These studies will provide new and
important information about how translational efficiency mechanisms promote the ability of a major human
fungal pathogen to both survive in the phagosome and lyse host macrophages. Ultimately, common fungal-
specif...

## Key facts

- **NIH application ID:** 9938421
- **Project number:** 5R21AI142560-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** DAVID KADOSH
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,840
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938421

## Citation

> US National Institutes of Health, RePORTER application 9938421, Regulation of Protein Synthesis During the C. albicans-Macrophage Interaction (5R21AI142560-02). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/9938421. Licensed CC0.

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