A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria
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Open Access
- 17 November 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 468 (7322), 439-442
- https://doi.org/10.1038/nature09490
Abstract
Contact-dependent growth inhibition (CDI), first described in Escherichia coli five years ago, is a mechanism by which cell-to-cell contact inhibits the growth of bacterial cells that do not have this system. CDI is mediated by the two-partner secretion proteins CdiA and CdiB, and a small immunity protein CdiI gives protection against autoinhibition. The molecular basis for some of the interactions involved in CDI has now been elucidated; the toxic properties of CdiA are contained within the protein's carboxy-terminal end (CdiA-CT). A search across other E. coli strains and bacterial species shows the system to be widespread — a range of bacteria contain one or more CdiA homologues, with varied CdiA-CT toxin sequences. These findings suggest that CDI systems constitute an intricate immunity network with an important function in bacterial growth competition in the environment. Contact-dependent growth inhibition (CDI) through a two-component system was first described in Escherichia coli as a mechanism to inhibit growth of bacterial cells that do not possess this system. Now the widespread occurrence of CDI in bacteria and the molecular basis for some of these interactions have been elucidated. The data suggest that CDI is a common mechanism by which microbes compete with each other in the environment. Bacteria have developed mechanisms to communicate and compete with one another in diverse environments1. A new form of intercellular communication, contact-dependent growth inhibition (CDI), was discovered recently in Escherichia coli2. CDI is mediated by the CdiB/CdiA two-partner secretion (TPS) system. CdiB facilitates secretion of the CdiA ‘exoprotein’ onto the cell surface. An additional small immunity protein (CdiI) protects CDI+ cells from autoinhibition2,3. The mechanisms by which CDI blocks cell growth and by which CdiI counteracts this growth arrest are unknown. Moreover, the existence of CDI activity in other bacteria has not been explored. Here we show that the CDI growth inhibitory activity resides within the carboxy-terminal region of CdiA (CdiA-CT), and that CdiI binds and inactivates cognate CdiA-CT, but not heterologous CdiA-CT. Bioinformatic and experimental analyses show that multiple bacterial species encode functional CDI systems with high sequence variability in the CdiA-CT and CdiI coding regions. CdiA-CT heterogeneity implies that a range of toxic activities are used during CDI. Indeed, CdiA-CTs from uropathogenic E. coli and the plant pathogen Dickeya dadantii have different nuclease activities, each providing a distinct mechanism of growth inhibition. Finally, we show that bacteria lacking the CdiA-CT and CdiI coding regions are unable to compete with isogenic wild-type CDI+ cells both in laboratory media and on a eukaryotic host. Taken together, these results suggest that CDI systems constitute an intricate immunity network with an important function in bacterial competition.Keywords
This publication has 14 references indexed in Scilit:
- Harpin Mediates Cell Aggregation in Erwinia chrysanthemi 3937Journal of Bacteriology, 2006
- Contact-Dependent Inhibition of Growth in Escherichia coliScience, 2005
- The Erwinia chrysanthemi EC16 hrp/hrc Gene Cluster Encodes an Active Hrp Type III Secretion System That Is Flanked by Virulence Genes Functionally Unrelated to the Hrp SystemMolecular Plant-Microbe Interactions®, 2004
- Analysis of Erwinia chrysanthemi EC16 pelE∷uidA, pelL∷uidA, and hrpN∷uidA Mutants Reveals Strain-Specific Atypical Regulation of the Hrp Type III Secretion SystemMolecular Plant-Microbe Interactions®, 2004
- Genetic Structure and Distribution of Four Pathogenicity Islands (PAI I 536 to PAI IV 536 ) of Uropathogenic Escherichia coli Strain 536Infection and Immunity, 2002
- Making sense of score statistics for sequence alignments.Briefings in Bioinformatics, 2001
- A bacterial two-hybrid system based on a reconstituted signal transduction pathwayProceedings of the National Academy of Sciences of the United States of America, 1998
- Improved allelic exchange vectors and their use to analyze 987P fimbria gene expressionGene, 1998
- Molecular Characterization of Pyocin S3, a Novel S-type Pyocin from Pseudomonas aeruginosaJournal of Biological Chemistry, 1995
- Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coliCell, 1994