# Mucosal determinants of Cryptosporidium infection

> **NIH NIH U19** · BAYLOR COLLEGE OF MEDICINE · 2021 · $440,083

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Okhuysen, Pablo C/Chappell, Cynthia L
Title: MUCOSAL DETERMINANTS OF CRYPTOSPORIDIUM INFECTION
PI: Pablo C. Okhuysen, MD
MD Anderson Cancer Center
PI (subcontract): Cynthia L. Chappell, PhD
UT School of Public Health
PROJECT SUMMARY
Cryptosporidium causes diarrheal illness and is second only to Rotavirus in prevalence among children in
developing areas. This environmentally resilient, highly infectious NIAID category B agent is also a major cause
of waterborne outbreaks of diarrhea in the US. In malnourished children, the elderly and in immunosuppressed
individuals, infection causes chronic debilitating illness that can be fatal. The parasite cannot be grown efficiently
in vitro and no effective treatment is available. New approaches to study the pathophysiology of this agent are
needed in order to develop strategies for treatment and control. We have previously shown that when exposed
to the parasite, healthy adult volunteers demonstrate distinct outcomes that are dependent on parasite
genotype/species. The molecular basis for these differences are unknown. We also recently showed that when
exposed to the parasite, volunteers with high levels of intestinal indole (IND), a gut bacterial product, are
protected from infection but nothing is known about why this association exists or its mechanism of action. Thus,
the overarching goal of this proposal is to examine potential mechanisms for the observed protective
phenomenon in the context of parasite genome diversity. To this end, we will use new techniques, such as full
length (FL) genome sequencing and organoid cultures, to examine the effect of microbiome composition and
IND compounds (ICs) on parasite infectivity in cell lines and intestinal organoid cultures. Genomic sequencing
and/or RNA expression of the host and/or parasite will help to delineate essential components of the host-
parasite interaction thereby suggesting potential interventions. Specifically, we will study the microbiome
composition and generate FL genomes from stool samples of: adults previously challenged with
Cryptosporidium; HIV-infected individuals; and immunosuppressed cancer patients, the latter two groups with
community-acquired Cryptosporidium. We will sequence parasite genomes and test the direct effects of ICs
on the parasite infectivity in cell lines and organoids by monitoring parasite binding, invasion, and replication.
We will also measure expression of cytokines and other immunomodulatory factors produced by infected cells
to better understand the role of the immune response in Cryptosporidium pathogenesis. Finally, in a proof of
concept experiment, we will deprive adult mice of IND, then challenge them with Cryptosporidium, and monitor
for infection. Metagenomic sequencing will monitor changes in the bacterial communities before and after
manipulation. Taken together, we expect these experiments will shed light on the mechanism involved in IND-
ass...

## Key facts

- **NIH application ID:** 10160782
- **Project number:** 5U19AI144297-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Pablo C Okhuysen
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $440,083
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160782

## Citation

> US National Institutes of Health, RePORTER application 10160782, Mucosal determinants of Cryptosporidium infection (5U19AI144297-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10160782. Licensed CC0.

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