# Two pathways for calcium signaling and virulence regulation in P. aeruginosa

> **NIH NIH P20** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2022 · $185,464

## Abstract

Abstract 
Pseudomonas aeruginosa is an opportunistic human pathogen that causes severe, life threatening infections in 
patients with cystic fibrosis (CF), endocarditis, wounds, artificial implants, and in healthcare-associated 
infections. The versatility of P. aeruginosa pathogenicity is associated with an outstanding physiological 
adaptability of the organism and its ability to modulate host responses, due in part to a tightly coordinated 
regulation of gene expression. Therefore, to gain control over currently untreatable Pseudomonas infections, it 
is critically important to generate new knowledge of the regulatory circuits coordinating the pathogen virulence 
in response to host factors. Calcium ion (Ca2+) is an essential intracellular messenger in eukaryotic cells, 
regulating vital cellular processes. It accumulates in pulmonary fluids of CF patients and in mitral annulus of 
endocarditis patients. Alterations in the host Ca2+ homeostasis may serve as a trigger for enhanced virulence 
of invading pathogens. In support, we showed that Ca2+ positively regulates biofilm formation, swarming, and 
production of several virulence factors in P. aeruginosa. However, the molecular mechanisms of such 
regulation are not known. It is also not known whether intracellular Ca2+ plays role as a second messenger in 
prokaryotes as it does in eukaryotes. Understanding the mechanisms of Ca2+ regulation, signaling and 
homeostasis will provide novel means for controlling P. aeruginosa viability, virulence, and interactions with the 
host. Earlier, we identified two putative Ca2+-binding proteins EfhP and CarP, mutations in which cause 
multiple Ca2+-dependent defects in virulence and infectivity. EfhP contains two EF-hand motives, known to 
bind Ca2+ and relay Ca2+ signal through conformational changes. CarP is predicted to form a beta-propeller and 
has a putative phytase domain. Based on the bioinformatics and preliminary studies, we hypothesize that 
EfhP and CarP provide different routes of Ca2+ signal transduction regulating virulence and host- 
pathogen interactions in response to Ca2+ in a host. To test this, we propose to determine the cellular 
localization and identify binding partners and signal-transducing pathways regulated by the two proteins. We 
will also characterize the role of EfhP and CarP in P. aeruginosa interactions with a host, and define their 
involvement in the development of acute and chronic infections. By utilizing the expertise of three OCRID core 
facilities, we will unravel the mechanisms of Ca2+ signaling and its role in regulating the ability of P. aeruginosa 
to cause infections at the molecular, cellular, and organismal level. This research is highly innovative as for 
the first time it will experimentally demonstrate Ca2+ signaling in bacteria, identify the components of Ca2+ signal 
transduction pathways, and define the role of Ca2+ signaling in P. aeruginosa pathogenicity in vivo.

## Key facts

- **NIH application ID:** 10459268
- **Project number:** 5P20GM103648-10
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** Marianna M. A. Patrauchan
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,464
- **Award type:** 5
- **Project period:** 2013-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459268

## Citation

> US National Institutes of Health, RePORTER application 10459268, Two pathways for calcium signaling and virulence regulation in P. aeruginosa (5P20GM103648-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10459268. Licensed CC0.

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