# Bacterial Interference to Prevent Staphylococcus aureus Infection

> **NIH NIH R01** · CHILDREN'S HOSP OF PHILADELPHIA · 2020 · $417,711

## Abstract

PROJECT SUMMARY
Although Staphylococcus aureus is a major human pathogen that causes an enormous
burden of disease, we have very few strategies for preventing infection or controlling its
spread. In the 1960's it was a widespread practice to inoculate neonates with a relatively
benign strain of S. aureus called 502A as a strategy to combat outbreaks of more
virulent staphylococcal strains, a practice referred to as bacterial interference.
Thousands of neonates were exposed to 502A with very little associated morbidity and
mortality, but despite its relatively good safety record, the practice was abandoned in the
1970's due to safety concerns. The basic mechanisms of bacterial interference were
never investigated. We recently showed that 502A elicits a very different cytokine
response compared to other epidemic and virulent strains. Although it is less invasive,
host cells exposed to 502A have increased levels of type I Interferons as well as several
other proinflammatory cytokines (eg., TNFa, IL-6) compared to exposure to other S.
aureus strains. Our hypothesis is that S. aureus strains that stimulate 502A-like
immune responses protect from colonization and subsequent infection by
inducing the immune system to reject other strains. Understanding the mechanism
of 502A bacterial interference could allow us to design strategies for protection against
colonization and infection with virulent or antibiotic resistant strains. It may also lead to
strategies for decolonization in the setting of recurrent S. aureus infection or in intensive
care units where universal decolonization using antimicrobials has been show to
decrease mortality. We combine a clinical approach with basic molecular research,
aiming to assess the feasibility of a bacterial interference strategy in the clinical context.
The study team integrates expertise in clinical S. aureus epidemiology, host innate
immunology, and genomics and microbiome studies. Aim 1 uses the natural diversity in
S. aureus strains found in human populations to prospectively assess the correlation of
colonization with 502A-like strains and possible protection. Aim 2 uses model systems
to assess the response of the immune system to 502A-like strains as well as their
protective effect. Aim 3 examines the possibility of using a virulence-attenuated strain
for bacterial interference and decolonization.

## Key facts

- **NIH application ID:** 9988909
- **Project number:** 5R01AI137526-03
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** PAUL J PLANET
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,711
- **Award type:** 5
- **Project period:** 2018-09-05 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988909

## Citation

> US National Institutes of Health, RePORTER application 9988909, Bacterial Interference to Prevent Staphylococcus aureus Infection (5R01AI137526-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9988909. Licensed CC0.

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