# In vivo essential genome of Salmonella

> **NIH NIH R03** · DIVISION OF AGRICULTURE · 2022 · $71,763

## Abstract

SUMMARY
Defining genome-wide genetic requirements for fitness of a bacterial pathogen in the host is a fundamental
goal of pathogenomics. Transposon sequencing (Tn-seq) is a power functional genomics tool for genome-wide
identification of essential and conditionally essential genes in bacteria. When applied to a bacterial pathogen
with an appropriate animal infection model, Tn-seq can accelerate the discovery of the genetic determinants of
a bacterial pathogen for in vivo fitness. However, the full potential of this powerful approach to understand
bacterial virulence determinants is often hampered by the bottlenecks associated with animal infection models.
The bottlenecks cause stochastic loss of the mutants without contribution of their genotypes, which can lead to
false positive discoveries. In this application, we will develop a novel strategy to overcome this limitation by
employing a transposon system that generates a genome-saturating random mutant library from the bacterial
cells multiplied from a small seeder population established in the target host tissue upon induction,
circumventing the bottleneck problem. The Tn-seq profile obtained from the genome-saturating mutant
population recovered from the host tissue would allow genome-wide identification of in vivo essential genes by
the genes lacking insertions in the same manner by which in vitro essential genes are identified. This new
approach will be fully developed and evaluated (Aim1) and applied for genome-wide identification of the gut
colonization factors of Salmonella Typhimurium 14028 during infection in mice (Aim 2). Once established and
validated, this approach can be easily extended to other bacterial pathogens to fully explore in vivo essential
genomes.

## Key facts

- **NIH application ID:** 10471446
- **Project number:** 5R03AI164158-02
- **Recipient organization:** DIVISION OF AGRICULTURE
- **Principal Investigator:** YOUNG MIN KWON
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $71,763
- **Award type:** 5
- **Project period:** 2021-08-18 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471446

## Citation

> US National Institutes of Health, RePORTER application 10471446, In vivo essential genome of Salmonella (5R03AI164158-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10471446. Licensed CC0.

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