# Calcium signaling controls Pseudomonas aeruginosa invasion and adaptation to the host intracellular environment

> **NIH NIH R15** · OKLAHOMA STATE UNIVERSITY STILLWATER · 2021 · $441,822

## Abstract

According to the World Health Organization (WHO) and the Center of Disease Control (CDC), Pseudomonas
aeruginosa is one of the critical priority pathogens, for which development of new treatments is urgently
needed. This pathogen causes lethal acute and chronic respiratory infections that represent one of the leading
causes of death worldwide. It is responsible for fatal infections in patients with cystic fibrosis (CF), endocarditis,
wounds, or patients with artificial implants. The versatility of P. aeruginosa pathogenicity is associated with an
outstanding physiological adaptability of the organism, which is due in part to a tightly coordinated regulation of
gene expression. Traditionally, P. aeruginosa was considered an extracellular pathogen with notorious ability
to form biofilms on living or artificial surfaces. However, recently the paradigm has shifted as P. aeruginosa
was shown to internalize into the cytoplasm of epithelial cells. Although studies on the mechanisms of
internalization are scarce, there is evidence of the importance of type 3 secretion system (T3SS) effectors. It
became obvious that in order to gain control over currently untreatable Pseudomonas infections, it is important
to not only understand the mechanisms of biofilm formation, but to also learn the regulatory circuits
coordinating the pathogen’s internalization and replication within host cells. Calcium (Ca2+) is a primary
intracellular messenger in eukaryotic cells, regulating most vital cellular processes. It is well known to control
the expression of T3SS effectors. Our published data indicate that Ca2+ regulates production of virulence
factors that contribute to the development of acute and chronic infections in P. aeruginosa. We showed that the
organism is able to maintain cellular Ca2+ homeostasis, and to produce Ca2+ transients in response to
extracellular factors, and identified several key components of Ca2+ signaling and regulatory network. Here, we
hypothesize that Ca2+-signaling plays a key role in regulating internalization of P. aeruginosa. To test this
hypothesis, we will (1) identify the genes differentially expressed in P. aeruginosa pre- and post-
internalization into epithelial cells; (2) determine the role of the key components of Ca2+ signaling in P.
aeruginosa internalization (3) monitor the temporal and spatial changes in Ca2+ subcellular
concentrations in P. aeruginosa during interactions with epithelial cells. The proposed research is
designed to provide an excellent training environment for undergraduate and graduate students. The
independent aims utilize an array of modern and well-established experimental approaches in molecular
microbiology and tissue culture. The research is innovative and significant because it will be first to study the
relationship between Ca2+-signaling and P. aeruginosa internalization. For the first time, we will characterize
the genome-wide changes in the pathogen’s gene expression upon internalization and identif...

## Key facts

- **NIH application ID:** 10292058
- **Project number:** 2R15GM124670-02
- **Recipient organization:** OKLAHOMA STATE UNIVERSITY STILLWATER
- **Principal Investigator:** Marianna M. A. Patrauchan
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $441,822
- **Award type:** 2
- **Project period:** 2017-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10292058

## Citation

> US National Institutes of Health, RePORTER application 10292058, Calcium signaling controls Pseudomonas aeruginosa invasion and adaptation to the host intracellular environment (2R15GM124670-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10292058. Licensed CC0.

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