title: A multidrug resistance plasmid contains the molecular switch for type VI secretion in Acinetobacter baumannii.
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.
authors.affiliation: Department 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;
authors.forename: Brent S
authors.initials: BS
authors.lastname: Weber
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G2;
authors.forename: Pek Man
authors.initials: PM
authors.lastname: Ly
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada T6G 2G2;
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Irwin
authors.affiliation: Department of Medical Microbiology and Immunology, Heritage Medical Research Center, University of Alberta, Edmonton, AB, Canada T6G 2S2.
authors.forename: Stefan
authors.initials: S
authors.lastname: Pukatzki
authors.affiliation: Department 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; mariofeldman@wustl.edu.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Feldman
mesh_terms: D040981:Acinetobacter baumannii / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry; D058947:Bacterial Secretion Systems / Q000235:genetics*; D001483:Base Sequence; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010641:Phenotype; D010957:Plasmids / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: D000900:Anti-Bacterial Agents; D058947:Bacterial Secretion Systems; D011994:Recombinant Proteins
keywords: Acinetobacter baumannii; T6SS; antibiotic resistance; bacterial secretion; plasmid