# Role of T6SS in plasmid-mediated MDR dissemination in Acinetobacter

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $196,614

## Abstract

PROJECT SUMMARY/ABSTRACT
Acinetobacter baumannii (Ab) is an opportunistic bacterium has an alarming predisposition to attain multi-drug
resistance (MDR), and infections with MDR-Ab strains are linked to greater morbidity and mortality. Ab is
categorized by the World Health Organization as a critical priority for the research and development of new
antimicrobial therapies. Plasmids serve as vehicles for the spread of MDR among Ab clinical isolates, and type
IV secretion system (T4SS)-dependent conjugation is an effective mean by which many of these plasmids are
disseminated. Acinetobacter contains three classes of plasmids: the Large Conjugative Plasmid (LCP), the
Medium-sized Conjugative Plasmid (MCP), and the small Mobilizable Plasmid (SMP) families. These plasmids
contain conserved T4SS machinery and/or elements that target them for mobilization, supporting that
conjugation plays a critical role in their dissemination. Successful T4SS-mediated conjugation requires close
contact between the plasmid “donor” strain and the plasmid “recipient” strain, as well as the subsequent
survival of the recipient. This is contrasted with the function of the Type-VI secretion system (T6SS), which
mediates indiscriminate, contact-dependent killing of neighboring, non-sister bacterial competitors. Most Ab
strains carry a constitutively active T6SS. This poses a unique challenge to conjugative plasmids, as Ab
plasmid “donors” can kill potential “recipients” and vice versa. However, Acinetobacter plasmids are
successfully disseminating, suggesting that they have evolved mechanisms to overcome this hypothetical
restriction. This proposal addresses the relationship between T6SS and plasmid conjugation in Ab. We
previously demonstrated that some LCPs have the unique ability to abrogate the expression of the T6SS
encoded in the host chromosome. Thus, we hypothesize that silencing the T6SS is essential for plasmid
conjugation and the resulting dissemination of multidrug resistance among Acinetobacter. Furthermore, we
propose that in the absence of their own conjugative machinery, horizontal transfer of SMPs relies on LCP-
encoded conjugation machineries and LCP-mediated T6SS repression. Because potential plasmid recipients
may employ their T6SS to kill potential plasmid donors, we propose that a constitutively active T6SS in
Acinetobacter can confer immunity against conjugation. Finally, we hypothesize that the role of conjugative
plasmids in MDR dissemination among Ab clinical isolates has gone largely unnoticed. This is likely due to the
limited understanding of Acinetobacter plasmid biology and the lack of a systematic epidemiological study of
their prevalence. Therefore, we propose a pilot prospective analysis to determine the incidence of conjugative
plasmids among contemporary Acinetobacter clinical isolates, their contribution to MDR, and their effects on
T6SS activity. This proposal may open new avenues to investigate innovative drugs with capacity of
eliminati...

## Key facts

- **NIH application ID:** 9878757
- **Project number:** 5R21AI144220-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Mario Feldman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,614
- **Award type:** 5
- **Project period:** 2019-02-21 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878757

## Citation

> US National Institutes of Health, RePORTER application 9878757, Role of T6SS in plasmid-mediated MDR dissemination in Acinetobacter (5R21AI144220-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878757. Licensed CC0.

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