# Investigation on Replicative aging in Cryptococcus neoformans populations

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $618,336

## Abstract

This application deals with a general problem in virulence of how pathogenic microbes adapt to and/or
escape host defenses and persist. Most infections are characterized by a complex relationship
between the host and the pathogen referred to as pathoadaptation. The system under study is based
on Cryptococcus neoformans (CN), a human pathogenic fungus that is a major cause of mortality and
morbidity in AIDS patients. This fungal infection is notoriously difficult to treat and despite effective
antifungal therapy mortality is high especially in AIDS patients with progressive disease. In the course
of a R21 funded research proposal we determined that replicating CN cells undergo asymmetric cell
divisions a process that leads to generational or replicative aging. CN cells undergo a finite number of
divisions before they die. The replicative life span (RLS) of a CN strain is a reproducible trait that can
be determined through micro-dissection. We found that CN cells of advanced replicative age (older)
persist during chronic infection because they are more resistant to hydrogen peroxide stress,
macrophage intracellular killing, and antifungal agents. We now propose to investigate the process of
replicative aging in more detail and specifically elucidate how the emerging properties of aging lead to
selection of older CN cells in the host, and contribute to persistence and virulence. Our proposal is
divided in three aims: I.) To investigate RLS dynamics in CN strains ii.) To investigate why old CN cells
are more resistant to antifungals and phagocytosis iii.) To investigate and model age dependent
resilience and vulnerability in vitro and in vivo.

## Key facts

- **NIH application ID:** 10107727
- **Project number:** 5R01AI127704-05
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Bettina Fries
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $618,336
- **Award type:** 5
- **Project period:** 2017-03-27 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10107727

## Citation

> US National Institutes of Health, RePORTER application 10107727, Investigation on Replicative aging in Cryptococcus neoformans populations (5R01AI127704-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10107727. Licensed CC0.

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