# Pathogenic Mechanism for Lung Infection in Mucoid Pseudomonas

> **NIH VA I01** · VA VETERANS ADMINISTRATION HOSPITAL · 2022 · —

## Abstract

ABSTRACT
Many VA patients are susceptible and succumb to infections with the opportunistic
pathogen, Pseudomonas aeruginosa. This can occur as a complication of COPD,
emphysema, chronic bronchitis, cancer and immunosuppressive drug therapy. Exposure
to this ubiquitous bacterium can result in nosocomial infections, which are common via
respiratory ventilators, catheters, lumbar punctures and general surgery. P. aeruginosa
is highly tolerant or resistant to most antibiotics, making it difficult to control such
infections, which leads to a high rate of morbidity/mortality. The goal of this research is
to improve our understanding of the biosynthesis and regulation of a protective capsule-
like polysaccharide called alginate, which is produced as a virulence factor by P.
aeruginosa. During chronic respiratory infections (e.g., COPD), adaptive mutations are
observed to occur in vivo that lead to the over production of this exopolysaccharide,
which confers a mucoid colony phenotype and resistance to phagocytic killing. This
suggests a high selective pressure for alginate production in the lung environment. Most
of the enzymes for the production of alginate are clustered in the large algD operon. The
mucoid phenotype is usually due to mutations that activate sigma-22. However, we have
discovered an alternate pathway for alginate production that involves a 2-component
regulator pair (AlgB-KinB) and sigma-54 (RpoN). Also, sigma-38 (RpoN) plays an
important role in alginate production, but this is not understood. Improving our
understanding of this pathogenic mechanism in P. aeruginosa will enhance the
management of pulmonary disease caused by this bacterium. In this study, we will: (1)
Determine the role of RpoN (sigma-54) in the control of alginate production, (2)
Determine the role of RpoS (sigma-38) in the control of alginate production and (3)
Identify drugs that enhance the phagocytosis of mucoid Pseudomonas as potential
therapeutic agents. The long-term goal of this research is to better understand alginate
production by P. aeruginosa as a critical virulence factor during pulmonary infection. The
information gained could be vital for the development of new therapeutic approaches in
the treatment of P. aeruginosa infections.

## Key facts

- **NIH application ID:** 10115323
- **Project number:** 2I01BX000477-09A2
- **Recipient organization:** VA VETERANS ADMINISTRATION HOSPITAL
- **Principal Investigator:** Dennis Edward Ohman
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2010-04-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115323

## Citation

> US National Institutes of Health, RePORTER application 10115323, Pathogenic Mechanism for Lung Infection in Mucoid Pseudomonas (2I01BX000477-09A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10115323. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*