# IRON, O2 AND IS ELEMENTS IN EXOTOXIN A EXPRESSION

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 1993 · $335,611

## Abstract

Pseudomonas aeruginosa is an important opportunistic pathogen both in
terms of the morbidity and mortality of infections it causes.  A
significant proportion of patients with cystic fibrosis (CF), are
colonized at an early age (l-2yrs) with this organism and most CF patients
ultimately succumb to a chronic lung infection from P. aeruginosa. The
reason for the extraordinary pathogenicity of P. aeruginosa in these
patients, as compared to other Pseudomonads for example, is not clear. It
is highly probable that the myriad of virulence determinants that P.
aeruginosa produces contributes to its pathogenic potential.
Unfortunately, the exact contribution of these factors, alone or in
combination, to even the simplest kind of P. aeruginosa infection has not
yet been elucidated. Moreover, the fact that expression of essentially all
of the identified major virulence determinants is regulated by a variety
of environmental conditions which the organism may encounter in the host
adds a great deal of complexity to analyzing the pathogenicity of P.
aeruginosa.  In the past few years studies using molecular, biochemical
and genetic approaches have begun to elucidate the mechanisms of
regulation of virulence determinants. A more comprehensive understanding
of regulatory processes involved in the expression of virulence
determinants could help in the rational development of effective measures
for the prevention and therapy of all kinds of P. aeruginosa infections.
The research described in this proposal is designed to fill gaps in our
knowledge regarding two specific issues salient to the pathogenic
potential of P. aeruginosa. The first relates to the mechanisms of how
environmental signals, specifically the concentration of environmental
iron and oxygen, regulate the expression of virulence determinants of P.
aeruginosa, particularly exotoxin A and protease. The mechanism by which
iron regulates the expression of these gene products is not completely
understood. Furthermore, while it has been known for many years that
oxygen regulates the expression of ETA, essentially nothing is known about
this mechanism of regulation. This oxygen regulation is particularly
relevant to the pathogenesis of P. aeruginosa in lung infections (e.g. in
CF patients) where oxygen therapy could regrettably enhance the expression
of virulence determinants such as ETA. The second issue to be addressed by
this research pertains to the isolation and further characterization of
insertion sequence (IS) elements that are unique to P. aeruginosa and are
localized to a region of the genome adjacent to the 5' end of the exotoxin
A gene (toxA). There is only a limited amount of information available
regarding the biology of IS elements unique P. aeruginosa, and essentially
nothing is known regarding their potential role in the expression of
pathogenicity. Molecular, genetic and biochemical approaches described in
this proposal will be used to examine both questions that are significant
to the pa...

## Key facts

- **NIH application ID:** 3126496
- **Project number:** 2R01AI015940-14
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **SAM.gov UEI:** MW8JHK6ZYEX8
- **Principal Investigator:** Michael L. Vasil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $335,611
- **Award type:** 2
- **Project period:** 1979-04-01 → 1998-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126496

## Citation

> US National Institutes of Health, RePORTER application 3126496, IRON, O2 AND IS ELEMENTS IN EXOTOXIN A EXPRESSION (2R01AI015940-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126496. Licensed CC0.

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