# Molecular Insights into the Uropathogenesis of MDR Acinetobacter baumannii

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $665,586

## Abstract

PROJECT SUMMARY/ABSTRACT
Multidrug resistant (MDR) infections caused by the bacterial pathogen Acinetobacter baumannii (Ab) are
increasing at alarming rates. Today the MDR frequencies among Ab clinical isolates are higher than any other
Gram-negative bacterium. For this reason, the World Health Organization has categorized Ab as top priority for
the research and development of new antimicrobial therapies. Ab is largely associated with healthcare-
acquired infections, namely pneumonia and septicemia. However, the ability of Ab to cause urinary tract
infections (UTI), including catheter-associated UTI (CAUTI), is underappreciated. Despite that 20-30% of the
Ab isolates come from urinary sources, there is no established model to study Ab UTI or the molecular basis of
uro-pathogenic Ab (UPAb) virulence. As UPAb are contributing to the rise of MDR UTI globally, there is a
pressing need to create new Ab UTI therapies. Thus, there is demand for a murine model to study MDR-UPAb
and to identify the bacterial factors critical for Ab UTI. We have developed the first Ab catheter-associated UTI
(CAUTI) murine model to examine implant and bladder colonization in mice, and we have selected the MDR
Ab isolate AbCA1 as model strain. AbCA1 was isolated from a female UTI patient in Argentina. The strain
belongs to the international Ab clone ST25, a phylogenetically distinct and emergently important lineage of Ab
clinical strains whose pathophysiology has been poorly studied. AbCA1 carries a large MDR-encoding plasmid,
pAB5, which belongs to a family of Ab Large Conjugative Plasmids (AbLCPs) identified in multiple,
geographically-diverse Ab strains. Interestingly, our preliminary findings show that pAB5 confers improved
survival in our CAUTI model, but reduced virulence in a pneumonia model. Adherence to the catheter and
urothelium constitutes the first stage in establishing CAUTI. We have validated our model showing that deletion
of chaperone-usher pili abrogates AbCA1 ability to colonize the catheter and bladder in our CAUTI model.
Similarly, deletion of the glycoprotease CpaA, one of the most abundantly expressed T2SS-associated
effector, diminished AbCA1 growth in human urine in vitro and virulence in the CAUTI model. In this
application, we propose to use our recognized expertise in Ab molecular biology and pathogenesis to
investigate the bacterial factors involved in the early stages of Ab CAUTI. We will further investigate the factors
involved in adherence and the extracellular and surface-exposed elements involved in UPAb pathogenesis.
We will also investigate how pAB5 enhances the uro-pathogenic state of AbCA1. Our work reveals that Ab is
not a homogenous group of pathogens with a stagnant battery of virulence factors; instead, strains appear to
acquire unique traits that better equip them to cause disease in specific host niches. Establishing a model Ab
strain and an animal disease model that represents these neglected infections is critical to efforts to ...

## Key facts

- **NIH application ID:** 9864036
- **Project number:** 5R01AI144120-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Mario Feldman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $665,586
- **Award type:** 5
- **Project period:** 2019-02-06 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864036

## Citation

> US National Institutes of Health, RePORTER application 9864036, Molecular Insights into the Uropathogenesis of MDR Acinetobacter baumannii (5R01AI144120-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864036. Licensed CC0.

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