A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii
Brent S Weber1, Pek Man Ly2, Joshua N Irwin2
1Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G2; Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110;
Abstract:
Infections with Acinetobacter baumannii, one of the most troublesome and least studied multidrug-resistant superbugs, are increasing at alarming rates. A. baumannii encodes a type VI secretion system (T6SS), an antibacterial apparatus of Gram-negative bacteria used to kill competitors. Expression of the T6SS varies among different strains of A. baumannii, for which the regulatory mechanisms are unknown. Here, we show that several multidrug-resistant strains of A. baumannii harbor a large, self-transmissible resistance plasmid that carries the negative regulators for T6SS. T6SS activity is silenced in plasmid-containing, antibiotic-resistant cells, while part of the population undergoes frequent plasmid loss and activation of the T6SS. This activation results in T6SS-mediated killing of competing bacteria but renders A. baumannii susceptible to antibiotics. Our data show that a plasmid that has evolved to harbor antibiotic resistance genes plays a role in the differentiation of cells specialized in the elimination of competing bacteria.
Insights
Multidrug-resistant Acinetobacter baumannii uses a resistance plasmid to control its type VI secretion system (T6SS). Plasmid loss activates T6SS to kill competitors, but increases antibiotic susceptibility in these superbug infections.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Acinetobacter baumannii is a problematic multidrug-resistant pathogen with increasing infection rates.
- This bacterium possesses a type VI secretion system (T6SS) for interbacterial competition.
- Regulatory mechanisms governing T6SS expression in A. baumannii remain largely unknown.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling type VI secretion system (T6SS) expression in multidrug-resistant Acinetobacter baumannii.
- To understand the role of resistance plasmids in the regulation of T6SS activity.
Main Methods:
- Analysis of multidrug-resistant Acinetobacter baumannii strains.
- Plasmid characterization and identification of genetic elements.
- Assessment of T6SS activity and antibiotic susceptibility.
Main Results:
- Multidrug-resistant A. baumannii strains harbor self-transmissible plasmids encoding negative regulators of the T6SS.
- T6SS activity is silenced in plasmid-carrying, antibiotic-resistant cells.
- Plasmid loss leads to T6SS activation, bacterial killing, and increased antibiotic susceptibility.
Conclusions:
- A resistance plasmid regulates T6SS activity in A. baumannii, influencing bacterial competition and antibiotic resistance.
- Plasmid-mediated regulation contributes to cell differentiation, with some cells specialized for killing competitors at the cost of antibiotic susceptibility.
- This mechanism highlights a novel role for resistance plasmids in bacterial population dynamics and virulence.
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