# High-Risk Clones of Pseudomonas aeruginosa

> **NIH NIH R21** · NORTHWESTERN UNIVERSITY · 2022 · $195,775

## Abstract

Project Summary
 Outbreaks of multidrug-resistant (MDR) Pseudomonas aeruginosa infections within medical institutions
have been commonly reported for many years. We now know that most of these outbreaks are caused by a
small group of widely dispersed MDR P. aeruginosa lineages, which are have been referred to as “high-risk
clones” (HRCs). HRCs are highly antibiotic resistant PA lineages that have spread across countries and even
continents to cause large numbers of infections. They emerged in the 1980s and 1990s and then rapidly
disseminated. The best characterized HRCs are the multilocus sequence types (MLSTs) ST235, ST175, and
ST111. HRCs are problematic for two reasons: (1) Because they readily spread within and between hospitals,
they cause a disproportionate number of infections. (2) They are highly resistant to antibiotics. In fact, it
appears that most MDR PA strains worldwide belong to these few HRC lineages. As expected, HRCs have
also been linked to particularly poor outcomes. What has allowed HRCs to spread so widely and to become so
resistant to antibiotics while the vast majority of P. aeruginosa STs are cultured only once and are antibiotic
susceptible? Relatively few experiments have been performed to address this important question, but
speculation has focused on two possibilities: (1) HRCs more effectively colonize the gastrointestinal (GI) tract
than other P. aeruginosa strains. The GI tracts of patients are a major reservoir for P. aeruginosa in the
hospital setting, and strains of P. aeruginosa capable of more effectively colonizing this niche would have a
considerable advantage in persisting and spreading to new patients within and between institutions. (2) HRCs
have properties that allow them to more efficiently acquire antibiotic resistance genes and alleles than
conventional P. aeruginosa strains. Populations of HRCs harbor an impressive array of mobile genetic
elements and chromosomal alleles that encode antibiotic resistance, suggesting that they are more amendable
to acquiring exogenous DNA and evolving mutations than conventional strains. We hypothesize that HRCs
are better able to colonize the GI tract and better able to acquire antibiotic-resistance determinants
than conventional P. aeruginosa strains. To test these hypotheses, we will perform the following Specific
Aims: (1) Use a mouse model to determine whether HRCs colonize the GI tract better than conventional P.
aeruginosa strains. (2) Determine whether HRCs have properties that allow them to more readily become
resistant to antibiotics. (3) Identify genetic loci that distinguish HRCs from conventional strains. Completion of
these aims will provide insights into the mechanisms by which HRCs persist in the hospital environment and
acquire MDR phenotypes. These insights in turn will highlight vulnerabilities that can be targeted by therapeutic
interventions that prevent the spread and limit the antibiotic resistance of HRCs. Such interventions would
impact not on...

## Key facts

- **NIH application ID:** 10408175
- **Project number:** 5R21AI164254-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ALAN R HAUSER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,775
- **Award type:** 5
- **Project period:** 2021-05-20 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408175

## Citation

> US National Institutes of Health, RePORTER application 10408175, High-Risk Clones of Pseudomonas aeruginosa (5R21AI164254-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408175. Licensed CC0.

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