identification of functional toxinimmunity genes linked to contact-dependent growth inhibition (cdi) and rearrangement hotspot (rhs) systems识别功能toxinimmunity基因与contact-dependent生长抑制(cdi)和重组热点(rhs)系统.pdfVIP

Identification of Functional Toxin/Immunity Genes Linked to Contact-Dependent Growth Inhibition (CDI) and Rearrangement Hotspot (Rhs) Systems 1 2 1 1 1 Stephen J. Poole *, Elie J. Diner , Stephanie K. Aoki , Bruce A. Braaten , Claire t’Kint de Roodenbeke , David A. Low1,2, Christopher S. Hayes1,2 1 Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara, Santa Barbara, California, United States of America, 2 Biomolecular Science and Engineering Program, University of California Santa Barbara, Santa Barbara, California, United States of America Abstract Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiA/CdiB family of two-partner secretion proteins. Each CdiA protein exhibits a distinct growth inhibition activity, which resides in the polymorphic C-terminal region (CdiA- CT). CDI+ cells also express unique CdiI immunity proteins that specifically block the activity of cognate CdiA-CT, thereby protecting the cell from autoinhibition. Here we show that many CDI systems contain multiple cdiA gene fragments that encode CdiA-CT sequences. These ‘‘orphan’’ cdiA-CT genes are almost always associated with downstream cdiI genes to form cdiA-CT/cdiI modules. Comparative genome analyses suggest that cdiA-CT/cdiI modules are mobile and exchanged between the CDI systems of different bacteria. In many instances, orphan cdiA-CT/cdiI modules are fused to full-length cdiA genes in other bacterial species. Examination of cdiA-CT/cdiI modules from Escherichia coli EC93, E. coli EC869, and Dickeya dadantii 3937 confirmed that these genes encode functional toxin/immunity pairs. Moreover, the orphan module from EC93 was functional in cell-mediated CDI when fused to the N-term