# Characterization of microbial and host requirements for colonic biofilm assembly and biofilm-mediated colon tumorigenesis

> **NIH NIH R00** · JOHNS HOPKINS UNIVERSITY · 2020 · $249,000

## Abstract

Sporadic colorectal cancer (CRC) remains a global health burden as one of the leading causes of cancer
and cancer-related deaths, and, strikingly, is also emerging as an acute health crisis in younger patients in
the US under the age of 50. These data suggest that novel efforts to identify contributors to the changing
landscape of CRC are urgently needed. In this R00 proposal, we seek to dissect the assembly and
tumorigenic mechanisms behind invasive, polymicrobial colonic biofilms, which were previously
established in the Sears laboratory to be a nearly universal feature of CRC tumors proximal to the hepatic
flexure. Biofilms were also identified on a subset (10-15%) of healthy patients without CRC, in whom
biofilms were associated with early, procarcinogenic changes, positing a role for bacterial biofilms in CRC
development. These biofilms were also associated with elevations in polyamine metabolites in mass
spectrometry-based analyses and induced a strong Interleukin-17 (IL-17) response in the mice by one
week, a cytokine signature associated with a worse prognosis in human CRC. Tissue slurries made from
human biofilms re-assembled into biofilms in the distal mouse colon; some - but not all – of these slurries
were directly tumorigenic in germ-free ApcMin/+ mice by 10-15 weeks. Extensive culturing of one
tumorigenic slurry following inoculation into mice revealed 35 bacterial isolates that, when re-inoculated
into additional mice, recapitulated the tumorigenesis of the original patient tumor slurry. Our specific aims
seek to build on these preliminary studies. Specific Aim (SA) 1 will identify the critical bacterial species
within the 35 isolate mixture that are responsible for biofilm formation and tumorigenesis. SA2 will test the
hypothesis that IL-17 and other immune parameters are critical mediators of biofilm formation and
biofilm-mediated tumorigenesis utilizing a combination of single-cell RNA sequencing, flow cytometry, and
qRT-PCR. Therapeutic modulation with an IL-17 antibody or knockout mice will be used to confirm the
requirement of IL-17 in biofilm formation and biofilm-mediated tumorigenesis. SA3 will utilize advanced
mass spectrometry methods to determine metabolites associated with biofilms in both patient and mouse
tissues and the localization of these metabolites in select samples. The experiments in this proposal will
provide valuable information regarding the host and microbial requirements for biofilm formation and
biofilm-mediated tumorigenesis that may lead to potential therapeutic targets or biomarkers for biofilms.

## Key facts

- **NIH application ID:** 10249484
- **Project number:** 4R00CA230192-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Julia L Drewes
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-09-01 → 2023-08-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249484

## Citation

> US National Institutes of Health, RePORTER application 10249484, Characterization of microbial and host requirements for colonic biofilm assembly and biofilm-mediated colon tumorigenesis (4R00CA230192-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10249484. Licensed CC0.

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