Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2017

Bacterial weapons of mass destruction: defining the type VI secretion system toxin arsenal of Acinetobacter baumannii (#130)

Timothy C Fitzsimons 1 , Jessica Lewis 2 , Deanna Deveson-Lucas 2 , Amy Wright 2 , Oded Kleifeld 3 , Ralf B Schittenhelm 3 4 , David Powell 5 , Marina Harper 2 , John D Boyce 2
  1. Microbiology, Monash University, Melbourne, VIC, Australia
  2. Microbiology, Monash University, Melbourne, VIC, Australia
  3. Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia
  4. Monash Biomedical Proteomics Facility, Monash University, Melbourne , VIC, Australia
  5. Monash Bioinformatics Platform, Monash University, Monash, Victoria, Australia

Acinetobacter baumannii is a Gram-negative bacterium that causes hospital-acquired infections. Many A. baumannii strains express a Type VI secretion system (T6SS), which is important for killing competitor strains. However, the T6SS toxins produced by different A. baumannii strains and the precise method of toxin delivery are poorly understood. T6SS toxins are often delivered together with VgrG proteins that form the tip of the T6SS needle. We analysed the A. baumannii AB307 genome and identified three vgrG genes, each located upstream of putative toxin and immunity genes. To confirm toxic activity, each gene (rhs1, rhs2 and lysM) was cloned independently into the arabinose-inducible E. coli plasmid pBAD-30. E. coli strains containing each construct were viable when expression was repressed, but not when expression was induced. To determine the role of each VgrG protein in toxin delivery, we generated vgrG1, vgrG2 and vgrG3 mutants. As each single vgrG mutant was predicted to still deliver two toxins, we also cloned pairs of immunity genes into the Acinetobacter plasmid pWH1266 and used these to transform the A. baylyi prey strain. The wild-type AB307 strain and all the single vgrG mutants were able to kill A. baylyi containing empty pWH1266. However, the vgrG1 mutant (predicted to deliver Rhs2 and LysM but not Rhs1) was unable to kill A. baylyi expressing the Rhs2I and LysMI immunity proteins, but could kill A. baylyi containing pwH1266 or pWH1266 expressing the other pairs of immunity proteins. Similar results were obtained for the vgrG2 and vgrG3 mutants. Therefore, we have shown that AB307-0294 delivers three T6SS toxins and one VgrG protein specifically carries one toxin. Analysis of all available A. baumannii genomes identified that each strain contains between two and four vgrG/toxin/antitoxin loci. Functional predictions indicate these toxins include peptidoglycan hydrolases, DNases, RNAses and a number with no clear function. We are currently probing the function of these predicted T6SS toxins to identify novel enzymes with antibacterial properties.