# Study of essential genes in Fusobacterium nucleatum

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $429,000

## Abstract

Project Summary: Fusobacterium nucleatum is a significant oral pathobiont associated with
periodontal diseases. When it spreads beyond the oral cavity, it is strongly linked to various
conditions, including colorectal cancer, adverse pregnancy outcomes, inflammatory bowel
disease, and rheumatoid arthritis. The current approaches to combat fusobacterial pathogenesis
have primarily involved antibiotic treatments, such as metronidazole. However, while these broad-
spectrum antibiotics are effective against F. nucleatum, they also disrupt the microbial balance,
leading to dysbiosis and further health complications. This underscores the need for more
targeted, narrow-spectrum antimicrobials that specifically inhibit or eradicate F. nucleatum. To
develop such targeted antibiotics, knowledge of the essential genes encoding core proteins
uniquely required for fusobacterial survival is needed. Our preliminary data show that fomA,
encoding the well-studied fusobacterial major outer membrane porin protein, is essential for cell
viability. This unexpected result challenges the previous report of its non-essential nature. Given
the colocalization of fomA with lysine degradation pathway-associated operons and the
substantial butyrate production by F. nucleatum via the lysine degradation pathway, we
hypothesized that FomA is an integral porin responsible for transporting butyrate, a by-product of
lysine degradation, from the periplasm to the cell's exterior. This proposal seeks to answer why
fomA is essential for cell survival and to systematically identify the essential genes in F. nucleatum,
with the long-term goal of developing targeted narrow-spectrum antibiotics against F. nucleatum.
Aim 1 will investigate the molecular basis of FomA's essentiality in F. nucleatum with a
comprehensive approach that includes a liposome swelling assay and a planar lipid biolayer
assay. Aim 2 will systematically identify the essential genes in F. nucleatum by high-density Tn5-
based transposon mutagenesis followed by high-throughput sequencing and create a CRISPRi
mutant library for each identified essential gene or operon. This experiment will define the nature
of fomA in F. nucleatum, along with a comprehensive understanding of its essentiome. Our
findings will pave the way for new, targeted, narrow-spectrum antibiotics to treat F. nucleatum
infections effectively.

## Key facts

- **NIH application ID:** 11036052
- **Project number:** 1R21DE034542-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Chenggang Wu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $429,000
- **Award type:** 1
- **Project period:** 2024-09-17 → 2026-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11036052

## Citation

> US National Institutes of Health, RePORTER application 11036052, Study of essential genes in Fusobacterium nucleatum (1R21DE034542-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11036052. Licensed CC0.

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