# Antagonistic relationships among Acinetobacter isolates

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $234,000

## Abstract

Nosocomial infections caused by gram-negative pathogens such as Acinetobacter baumannii have become a
major challenge in the treatment of immunocompromised individuals and patients with traumatic injuries. These
infections include ventilator-associated pneumonia, catheter-related urinary tract infections and non-healing
wound infections that can ultimately lead to sepsis. Of significant concern is the increasing frequency of life-
threatening infections caused by drug resistant A baumannii, reinforcing the need for new therapeutic
approaches. Recent studies have shown that A. baumannii taxa are abundant in clinical environments and that
decreases in microbial diversity contribute to increased antimicrobial resistance. However, little is known about
the biological and physical interactions between Acinetobacter sp isolated from these environments.
Characterization of a growing collection of Acinetobacter isolates obtained directly from patients at the University
of Michigan Hospital System over a period of 5 years has identified “predator” strains of A. baumannii capable
of inhibiting the growth of susceptible (“prey”) Acinetobacter strains. This phenotype is manifested as a zone of
clearing of susceptible bacteria – embedded in soft agar - that emanates from centrally inoculated predator
strains. Crude extracts containing a novel peptide toxin belonging to the family of ribosomally synthesized and
posttranslationally modified peptides (RiPPs) can be isolated from the predator and subsequently added to prey
strains resulting in cell contact-independent growth inhibition. Our preliminary data demonstrate that the
presence of the genes predicted to be required for the synthesis, modification, and secretion of this RiPP, a
novel peptide toxin, is relatively rare. Screening of our strain collection indicate that approximately 3 % carry the
genes and display the growth inhibition phenotype. Analysis of available sequences in the NCBI database
confirms the relatively scarceness of these genes. In contrast, several A. baumannii strains including multidrug
resistant A. baumannii isolates as well as strains of the species Acinetobacter pittii are sensitive to killing. The
primary objective of this study is to dissect these antagonistic interactions among Acinetobacter isolates. We aim
to determine the nature of the peptide toxin and its mechanism of secretion. In addition, experiments are
designed to reveal how the toxin enters susceptible strains and by what mechanism it inhibits their growth. These
studies will advance our understanding of the role of the toxin and have significant translational implications with
potential for precision drug therapy as the use of the toxin or variants thereof may represent a promising means
of combating infections caused by multi-drug resistant A. baumannii.

## Key facts

- **NIH application ID:** 10734782
- **Project number:** 5R21AI174418-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Maria B Sandkvist
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2022-11-04 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10734782

## Citation

> US National Institutes of Health, RePORTER application 10734782, Antagonistic relationships among Acinetobacter isolates (5R21AI174418-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10734782. Licensed CC0.

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