# Rational identification of Corynebacterium strains for use as probiotics

> **NIH NIH R21** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2022 · $245,116

## Abstract

Project Summary
Pneumonia is the leading infectious killer of children. Bacterial pathogens, particularly Streptococcus
pneumoniae, cause the most serious disease and mortality. Vaccination reduces invasive diseases such as
bacteremia and meningitis caused by vaccine serotypes. However, vaccination does not equally lower the
burden of pneumonia, and non-vaccine S. pneumoniae serotypes continue to emerge to cause respiratory and
invasive infections. Thus, an opportunity exists for new ways to prevent these infections.
Nasopharyngeal colonization precedes bacterial pneumonia and other respiratory infections, and the microbiota
serves as a barrier to pathogen colonization and subsequent invasion of the lower respiratory tract. Our studies
and others demonstrate that commensal, non-pathogenic Corynebacterium species are associated with a lower
prevalence of colonization by bacterial respiratory pathogens, including S. pneumoniae. The data show an
inverse correlation between the relative abundance of Corynebacterium in the nasopharyngeal microbiota and
the risk of colonization by S. pneumoniae. These Corynebacterium species may be promising biotherapeutic
candidates for development if they exert specific mechanistic control of bacterial respiratory pathogens.
The overall objective herein is to identify the mechanisms by which Corynebacterium spp. colonize the human
nasopharynx and exclude S. pneumoniae colonization. The rationale is that defining the mechanisms of these
interspecies interactions will lead to identifying Corynebacterium spp. that exert multiple mechanisms of
pathogen exclusion and are candidates for future biotherapeutics to prevent respiratory infections.
The Specific Aims are: 1) Identify mechanisms by which Corynebacterium spp. adhere to the respiratory
epithelium and inhibit Sp colonization through competitive adherence, and 2) Elucidate non-adherence
mechanisms by which Corynebacterium spp. inhibit Sp colonization. This proposal will combine models of
bacteria-host and bacteria-bacteria interactions to define mechanisms through which Corynebacterium inhibit S.
pneumoniae colonization. We will leverage comparative genomics of a large Corynebacterium strain repository
to identify accessory gene candidates that mediate respiratory epithelium attachment, competitive adherence
with S. pneumoniae, and pneumococcal growth inhibition through secreted factors.
The impact of this work is expected from the mechanistic insights and Corynebacterium strain identification
that may lead to the first rationally-designed biotherapeutics to prevent pneumonia and other respiratory
infections.

## Key facts

- **NIH application ID:** 10453307
- **Project number:** 1R21AI154081-01A1
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Matthew Scott Kelly
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $245,116
- **Award type:** 1
- **Project period:** 2022-05-16 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10453307

## Citation

> US National Institutes of Health, RePORTER application 10453307, Rational identification of Corynebacterium strains for use as probiotics (1R21AI154081-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10453307. Licensed CC0.

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