# Elucidating how CRISPR-Cas Modulates the Spread of S. aureus Pathogenicity Islands

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $51,752

## Abstract

PROJECT SUMMARY/ABSTRACT
Staphylococcus aureus is a major cause of both community-acquired and nosocomial infections, which have
become increasingly challenging to treat due to the widespread evolution of antimicrobial resistance. There is a
critical need for the development of alternative therapeutic approaches against multidrug-resistant bacteria that
also spare the protective commensal microbiota, which often provide colonization resistance against pathogens.
Bacterial disease is driven by S. aureus toxins and other virulence factors, which are mainly encoded by mobile
genetic elements (MGEs). In particular, numerous enterotoxins and the superantigen toxin causing Toxic Shock
Syndrome are all carried by a class of MGEs called the S. aureus Pathogenicity Islands (SaPIs), which spread
between bacteria by hijacking the reproductive machinery of bacteriophages. Staphylococci also possess
CRISPR-Cas systems, which provide adaptive immunity by blocking invading MGEs like phages and plasmids.
In this proposal, building upon preliminary data, I will test the central hypothesis that CRISPR-Cas systems also
prevent the transmission of SaPI elements and their associated virulence genes. In Aim 1, I will define the
complex tripartite interplay between staphylococcal CRISPR systems, SaPIs, and their helper phages using
various molecular and genetic approaches. In Aim 2, I will investigate the mechanisms by which SaPIs manage
to overcome CRISPR-mediated restriction and disseminate throughout bacterial populations. I anticipate that
these studies will elucidate both the molecular basis and biological consequences for CRISPR-SaPI interactions.
In Aim 3, I will evaluate whether CRISPR can be used to selectively kill SaPI-harboring S. aureus and establish
a proof-of-concept for CRISPR-based antimicrobials directed against virulence-encoding MGEs. The proposed
experiments will contribute to the long-term goal of designing alternative therapeutic approaches in an effort to
overcome the shortcomings of antibiotics in treating multidrug-resistant infections. This fellowship will support
my training in the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, including my
doctoral work in the laboratory of Dr. Luciano Marraffini at Rockefeller and the remainder of my medical training
at Weill Cornell. The training plan outlined in this fellowship project is designed to optimally prepare me for a
research career as an independent principal investigator and physician-scientist.

## Key facts

- **NIH application ID:** 10473519
- **Project number:** 5F30AI157535-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Dalton Van Banh
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2021-08-06 → 2025-08-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473519

## Citation

> US National Institutes of Health, RePORTER application 10473519, Elucidating how CRISPR-Cas Modulates the Spread of S. aureus Pathogenicity Islands (5F30AI157535-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10473519. Licensed CC0.

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