title: The toxin/immunity network of Burkholderia pseudomallei contact-dependent growth inhibition (CDI) systems.
abstract: Burkholderia pseudomallei is a category B pathogen and the causative agent of melioidosis--a serious infectious disease that is typically acquired directly from environmental reservoirs. Nearly all B. pseudomallei strains sequenced to date (> 85 isolates) contain gene clusters that are related to the contact-dependent growth inhibition (CDI) systems of γ-proteobacteria. CDI systems from Escherichia coli and Dickeya dadantii play significant roles in bacterial competition, suggesting these systems may also contribute to the competitive fitness of B. pseudomallei. Here, we identify 10 distinct CDI systems in B. pseudomallei based on polymorphisms within the cdiA-CT/cdiI coding regions, which are predicted to encode CdiA-CT/CdiI toxin/immunity protein pairs. Biochemical analysis of three B. pseudomallei CdiA-CTs revealed that each protein possesses a distinct tRNase activity capable of inhibiting cell growth. These toxin activities are blocked by cognate CdiI immunity proteins, which specifically bind the CdiA-CT and protect cells from growth inhibition. Using Burkholderia thailandensis E264 as a model, we show that a CDI system from B. pseudomallei 1026b mediates CDI and is capable of delivering CdiA-CT toxins derived from other B. pseudomallei strains. These results demonstrate that Burkholderia species contain functional CDI systems, which may confer a competitive advantage to these bacteria.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA.
authors.forename: Kiel
authors.initials: K
authors.lastname: Nikolakakis
authors.forename: Saba
authors.initials: S
authors.lastname: Amber
authors.forename: J Scott
authors.initials: JS
authors.lastname: Wilbur
authors.forename: Elie J
authors.initials: EJ
authors.lastname: Diner
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Aoki
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Poole
authors.forename: Apichai
authors.initials: A
authors.lastname: Tuanyok
authors.forename: Paul S
authors.initials: PS
authors.lastname: Keim
authors.forename: Sharon
authors.initials: S
authors.lastname: Peacock
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Hayes
authors.forename: David A
authors.initials: DA
authors.lastname: Low
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D016957:Burkholderia pseudomallei / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D003260:Contact Inhibition; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008554:Melioidosis / Q000276:immunology* / Q000382:microbiology*; D005810:Multigene Family
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004722:Endoribonucleases