# MECHANISTIC CHARACTERIZATION OF A NOVEL ATTACHMENT PROTEIN IN PSEUDOMONAS AERUGINOSA

> **NIH NIH R21** · UNIVERSITY OF HAWAII AT MANOA · 2020 · $176,875

## Abstract

PROJECT SUMMARY
 Biofilm formation represents a protective mode of growth that allows microorganisms to survive in
hostile environments and disperse cells to colonize new niches under desirable conditions. When established
at undesired locations, these microbial communities are of great concern clinically and industrially, in part due
to their ability to tolerate a wide range of treatment and eradication strategies. A better understanding of the
genetic and molecular mechanisms of biofilm formation and maintenance may provide novel treatment
strategies for the control of chronic infections and problems related to biofilm.
 Utilizing our recently developed single bacterium transcriptomic analysis technology, a Pseudomonas
aeruginosa spatial gene expression profile in three distinct locations in the biofilm architecture was obtained
(i.e., surface, middle, and interior of the biofilm structure). A previously uncharacterized hypothetical protein
PA3966, spatially up-regulated in the interior of the biofilm, is shown to be essential for biofilm formation and in
vivo pathogenesis in both mouse lung and fruit fly infection models. Additionally, PA3966 was up-regulated
during chronic lung infections of cystic fibrosis patients, highlighting the significance of this protein. Further
characterizations of PA3966 suggested that it is a potential attachment protein and specifically binds to two
human cell lines, lung epithelial A549 cells and embryonic kidney HEK293T cells.
 In this study, we are proposing one aim to characterize the molecular mechanisms of this novel
attachment protein. Aim 1A will identify the spatial and temporal expression patterns of PA3966 and its
essential region(s) for attachment function. Aim 1B aims to validate the attachment specificity of PA3966 to
host cells and identify its host cell receptor(s). Detailed characterizations of this recently discovered attachment
protein PA3966 could provide potential drug-target and alternative therapeutic strategies toward better
treatment outcome of bacterial biofilm related infections.

## Key facts

- **NIH application ID:** 9937655
- **Project number:** 5R21AI140071-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Yun Heacock-Kang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $176,875
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937655

## Citation

> US National Institutes of Health, RePORTER application 9937655, MECHANISTIC CHARACTERIZATION OF A NOVEL ATTACHMENT PROTEIN IN PSEUDOMONAS AERUGINOSA (5R21AI140071-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9937655. Licensed CC0.

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