# Regulation in Fusobacterium-mediated coaggregation

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $326,781

## Abstract

PROJECT SUMMARY
Dental plaque and associated periodontal diseases represent a common infectious disease afflicting nearly
half of American adults (CDC). The complex intra- and interspecies interactions regulate the development of
multispecies oral microbial communities called dental plaque. The dental plaque is made of an organized,
highly complex microbial social community and the Gram-negative anaerobe F.nucleatum is a key organism of
this microbiome by virtue of its unique capability to physically aggregate with many early and late colonizers.
Besides its role in periodontitis, F. nucleatum has been linked to several extra-oral diseases including preterm
birth and colorectal cancer. Although the fusobacterial interactions with other bacteria have been widely
studied and four coaggregation adhesins identified, little is known about mechanisms that regulate
Fusobacterium-mediated coaggregation, mainly due to the lack of a robust genetic toolkit for manipulation of F.
nucleatum. To overcome this, we recently developed a convenient gene deletion system for F. nucleatum and
generated a large library of random transposon mutants with ~10-fold genome coverage. Screening of this
library uncovered several coaggregation factors, which include a unique two-component system termed CarS-
CarR and a nine-gene-operon that encodes a lysine-degrading pathway (LDP) that controls the amount and
activity of RadD, respectively. RadD, a type IV autotransporter, is a versatile adhesin that mediates
fusobacterial adhesion with many early and some late colonizers. Based on these findings, we plan to
characterize the two regulatory factors in-depth. We will be the first time to show an oral bacterial two
component signaling component regulates expression of cell-cell adhesin in a cell density-dependent manner
and characterize a lysine riboswitch related to lysine catabolism in bacteria. Upon the successful completion of
this research, we expect to have significantly contributed to the understanding of how the versatile adhesin
RadD is regulated by identifying and deciphering factors and mechanism involved. Because RadD requires F.
nucleatum to incorporate into an established community made of initial commensal colonizers, such as
streptococci and actinomyces, our discoveries will have a significant impact on the understanding of
fusobacterium-mediated coaggregation role in development of dental plaque, will provide new insights into the
development of potent therapeutic strategies against this important pathogen.

## Key facts

- **NIH application ID:** 10847503
- **Project number:** 5R01DE030895-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Chenggang Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $326,781
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847503

## Citation

> US National Institutes of Health, RePORTER application 10847503, Regulation in Fusobacterium-mediated coaggregation (5R01DE030895-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10847503. Licensed CC0.

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