# The role of NosP in Pseudomonas aeruginosa biofilm development

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $336,496

## Abstract

Bacterial biofilms are a considerable public health threat because they cause chronic and hospital-acquired
infections, as well as the persistent biofouling of medical implants, but are resistant to antibiotics. Biofilm
regulation by NO has been observed broadly in bacteria, thus therapeutic interventions based on NO signaling
could have a significant impact on public health. Bacterial NO signaling is poorly understood, however. For
example, NO regulation of biofilm dispersal in P. aeruginosa, a principal pathogen in cystic fibrosis and
hospital-acquired infections, is very well documented, but the NO sensor remains unknown. To bridge this
knowledge gap, a long-term goal of the PI is to determine the mechanism of NO signaling in bacteria and to
use this knowledge as a foundation for developing therapeutic strategies to disperse biofilms. The PI has
shown that NO regulates biofilm formation in many bacteria, including P. aeruginosa, but P. aeruginosa lack a
homolog of the H-NOX protein shown to mediate the response to NO in other species. Thus, P. aeruginosa
must have an alternate NO sensor. The PI has discovered a novel family of hemoproteins named NosP. Based
on strong preliminary data it is hypothesized that NosP is a NO sensor that regulates biofilm formation. The
objective of the proposed work is to characterize P. aeruginosa NosP and determine the role of this protein in
NO-mediated control of biofilm formation. This proposal is innovative because it forges new logical connections
between NO sensing and biofilm formation, establishing a new paradigm for the role of NO in bacteria. This
proposal is significant because elucidation of the basis for NO signaling in P. aeruginosa will open new
therapeutic opportunities for controlling infection caused by this important human pathogen. The hypothesis
will be tested by pursuing three specific aims: (1) to determine the phenotype of nosP; (2) to gain structural and
functional insights into NosP; and (3) to delineate the signaling mechanism downstream of NosP. Under aim 1,
P. aeruginosa biofilm, virulence, and antibiotic resistance will be quantified in the presence of varying amounts
of NO, using wild-type and NosP deletion and expression strains. Under aim 2, the structure and spectroscopy
of NosP will be described and it will be determined if NosP reversibly binds NO concentrations consistent with
biofilm dispersal. Under aim 3, it will be determined if NosP regulates the activity of a certain kinase to mediate
biofilm formation through HptB/sRNA signaling. The PI has significant experience with the proposed assays.
Upon completion of these aims, NosP is expected to be established as an NO sensor that regulates biofilm
formation in P. aeruginosa. This would be a fundamentally important discovery because it will define a new
signaling pathway and novel antibiotic targets, for which there is a pressing need, especially in light of the
increased antibiotic resistance typically seen in biofilming orga...

## Key facts

- **NIH application ID:** 9856890
- **Project number:** 5R01GM118894-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** ELIZABETH M BOON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,496
- **Award type:** 5
- **Project period:** 2017-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856890

## Citation

> US National Institutes of Health, RePORTER application 9856890, The role of NosP in Pseudomonas aeruginosa biofilm development (5R01GM118894-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856890. Licensed CC0.

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