scholarly journals Identification of Functional Toxin/Immunity Genes Linked to Contact-Dependent Growth Inhibition (CDI) and Rearrangement Hotspot (Rhs) Systems

PLoS Genetics ◽  
2011 ◽  
Vol 7 (8) ◽  
pp. e1002217 ◽  
Author(s):  
Stephen J. Poole ◽  
Elie J. Diner ◽  
Stephanie K. Aoki ◽  
Bruce A. Braaten ◽  
Claire t'Kint de Roodenbeke ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Immunity Genes ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

scholarly journals Escherichia coli EC93 deploys two plasmid-encoded class I contact-dependent growth inhibition systems for antagonistic bacterial interactions

2021 ◽  
Author(s):  
Marcus Wäneskog ◽  
Tiffany Halvorsen ◽  
Klara Filek ◽  
Feifei Xu ◽  
Disa L. Hammarlöf ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Growth Inhibition ◽  
Type Species ◽  
Target Cells ◽  
Content Type ◽  
E Coli ◽  
Link Type ◽  
Immunity Genes ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

The phenomenon of contact-dependent growth inhibition (CDI) and the genes required for CDI (cdiBAI) were identified and isolated in 2005 from an Escherichia coli isolate (EC93) from rats. Although the cdiBAI EC93 locus has been the focus of extensive research during the past 15 years, little is known about the EC93 isolate from which it originates. Here we sequenced the EC93 genome and find two complete and functional cdiBAI loci (including the previously identified cdi locus), both carried on a large 127 kb plasmid. These cdiBAI systems are differentially expressed in laboratory media, enabling EC93 to outcompete E. coli cells lacking cognate cdiI immunity genes. The two CDI systems deliver distinct effector peptides that each dissipate the membrane potential of target cells, although the two toxins display different toxic potencies. Despite the differential expression and toxic potencies of these CDI systems, both yielded similar competitive advantages against E. coli cells lacking immunity. This can be explained by the fact that the less expressed cdiBAI system (cdiBAIEC93-2 ) delivers a more potent toxin than the highly expressed cdiBAIEC93-1 system. Moreover, our results indicate that unlike most sequenced CDI+ bacterial isolates, the two cdi loci of E. coli EC93 are located on a plasmid and are expressed in laboratory media.

scholarly journals New Players in the Toxin Field: Polymorphic Toxin Systems in Bacteria

mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Anne Jamet ◽  
Xavier Nassif
Keyword(s):  
In Silico ◽  
Bacterial Strains ◽  
Secretion Systems ◽  
Toxic Activity ◽  
New Family ◽  
Small Proteins ◽  
Immunity Genes ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition ◽  
Terminal Domains

ABSTRACTBacteria have evolved numerous strategies to increase their competitiveness and fight against each other. Indeed, a large arsenal of antibacterial weapons is available in order to inhibit the proliferation of competitor cells. Polymorphic toxin systems (PTS), recently identified by bioinformatics in all major bacterial lineages, correspond to such a system primarily involved in conflict between related bacterial strains. They are typically composed of a secreted multidomain toxin, a protective immunity protein, and multiple cassettes encoding alternative toxic domains. The C-terminal domains of polymorphic toxins carry the toxic activity, whereas the N-terminal domains are related to the trafficking mode.In silicoanalysis of PTS identified over 150 distinct toxin domains, including putative nuclease, deaminase, or peptidase domains. Immunity genes found immediately downstream of the toxin genes encode small proteins that protect bacteria against their own toxins or against toxins secreted by neighboring cells. PTS encompass well-known colicins and pyocins, contact-dependent growth inhibition systems which include CdiA and Rhs toxins and some effectors of type VI secretion systems. We have recently characterized the MafB toxins, a new family of PTS deployed by pathogenicNeisseriaspp. Many other putative PTS have been identified byin silicopredictions but have yet to be characterized experimentally. However, the high number of these systems suggests that PTS have a fundamental role in bacterial biology that is likely to extend beyond interbacterial competition.

scholarly journals Structural insight into toxin secretion by contact-dependent growth inhibition transporters

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeremy Guerin ◽  
Istvan Botos ◽  
Zijian Zhang ◽  
Karl Lundquist ◽  
James C Gumbart ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Outer Membrane ◽  
Structural Modifications ◽  
Extracellular Loops ◽  
Toxin Secretion ◽  
Dependent Growth ◽  
Α Helix ◽  
Dynamics Simulations ◽  
Outer Membrane Transporters ◽  
Contact Dependent Growth Inhibition

Bacterial contact-dependent growth inhibition (CDI) systems use a type Vb secretion mechanism to export large CdiA toxins across the outer membrane by dedicated outer membrane transporters called CdiB. Here, we report the first crystal structures of two CdiB transporters from Acinetobacter baumannii and Escherichia coli. CdiB transporters adopt a TpsB fold, containing a 16-stranded transmembrane β-barrel connected to two periplasmic domains. The lumen of the CdiB pore is occluded by an N-terminal α-helix and the conserved extracellular loop 6; these two elements adopt different conformations in the structures. We identified a conserved DxxG motif located on strand β1 that connects loop 6 through different networks of interactions. Structural modifications of DxxG induce rearrangement of extracellular loops and alter interactions with the N-terminal α-helix, preparing the system for α-helix ejection. Using structural biology, functional assays, and molecular dynamics simulations, we show how the barrel pore is primed for CdiA toxin secretion.

scholarly journals Genetic Evidence for SecY Translocon-Mediated Import of Two Contact-Dependent Growth Inhibition (CDI) Toxins

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allison M. Jones ◽  
Petra Virtanen ◽  
Disa Hammarlöf ◽  
William J. Allen ◽  
Ian Collinson ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Target Cell ◽  
Bacterial Species ◽  
Genetic Evidence ◽  
Target Cells ◽  
Content Type ◽  
Sec Translocon ◽  
Dependent Growth ◽  
Cell Envelopes ◽  
Contact Dependent Growth Inhibition

ABSTRACT The C-terminal (CT) toxin domains of contact-dependent growth inhibition (CDI) CdiA proteins target Gram-negative bacteria and must breach both the outer and inner membranes of target cells to exert growth inhibitory activity. Here, we examine two CdiA-CT toxins that exploit the bacterial general protein secretion machinery after delivery into the periplasm. A Ser281Phe amino acid substitution in transmembrane segment 7 of SecY, the universally conserved channel-forming subunit of the Sec translocon, decreases the cytotoxicity of the membrane depolarizing orphan10 toxin from enterohemorrhagic Escherichia coli EC869. Target cells expressing secYS281F and lacking either PpiD or YfgM, two SecY auxiliary factors, are fully protected from CDI-mediated inhibition either by CdiA-CTo10EC869 or by CdiA-CTGN05224, the latter being an EndoU RNase CdiA toxin from Klebsiella aerogenes GN05224 that has a related cytoplasm entry domain. RNase activity of CdiA-CTGN05224 was reduced in secYS281F target cells and absent in secYS281F ΔppiD or secYS281F ΔyfgM target cells during competition co-cultures. Importantly, an allele-specific mutation in secY (secYG313W) renders ΔppiD or ΔyfgM target cells specifically resistant to CdiA-CTGN05224 but not to CdiA-CTo10EC869, further suggesting a direct interaction between SecY and the CDI toxins. Our results provide genetic evidence of a unique confluence between the primary cellular export route for unfolded polypeptides and the import pathways of two CDI toxins. IMPORTANCE Many bacterial species interact via direct cell-to-cell contact using CDI systems, which provide a mechanism to inject toxins that inhibit bacterial growth into one another. Here, we find that two CDI toxins, one that depolarizes membranes and another that degrades RNA, exploit the universally conserved SecY translocon machinery used to export proteins for target cell entry. Mutations in genes coding for members of the Sec translocon render cells resistant to these CDI toxins by blocking their movement into and through target cell membranes. This work lays the foundation for understanding how CDI toxins interact with the protein export machinery and has direct relevance to development of new antibiotics that can penetrate bacterial cell envelopes.

scholarly journals Spatial Organization of Expanding Bacterial Colonies Is Affected by Contact-Dependent Growth Inhibition

2019 ◽  
Vol 29 (21) ◽  
pp. 3622-3634.e5 ◽  
Author(s):  
Michael J. Bottery ◽  
Ioannis Passaris ◽  
Calvin Dytham ◽  
A. Jamie Wood ◽  
Marjan W. van der Woude
Keyword(s):  
Growth Inhibition ◽  
Spatial Organization ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

scholarly journals Contact-Dependent Growth Inhibition (CDI) and CdiB/CdiA Two-Partner Secretion Proteins

2015 ◽  
Vol 427 (23) ◽  
pp. 3754-3765 ◽  
Author(s):  
Julia L.E. Willett ◽  
Zachary C. Ruhe ◽  
Celia W. Goulding ◽  
David A. Low ◽  
Christopher S. Hayes
Keyword(s):  
Growth Inhibition ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

scholarly journals Interbacterial signaling via Burkholderia contact-dependent growth inhibition system proteins

2016 ◽  
Vol 113 (29) ◽  
pp. 8296-8301 ◽  
Author(s):  
Erin C. Garcia ◽  
Andrew I. Perault ◽  
Sara A. Marlatt ◽  
Peggy A. Cotter
Keyword(s):  
Growth Inhibition ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Model Organism ◽  
Protein Toxin ◽  
Naturally Occurring ◽  
Catalytically Active ◽  
Dependent Growth ◽  
Underlying Mechanisms ◽  
Contact Dependent Growth Inhibition

In prokaryotes and eukaryotes, cell–cell communication and recognition of self are critical to coordinate multicellular functions. Although kin and kind discrimination are increasingly appreciated to shape naturally occurring microbe populations, the underlying mechanisms that govern these interbacterial interactions are insufficiently understood. Here, we identify a mechanism of interbacterial signal transduction that is mediated by contact-dependent growth inhibition (CDI) system proteins. CDI systems have been characterized by their ability to deliver a polymorphic protein toxin into the cytoplasm of a neighboring bacterium, resulting in growth inhibition or death unless the recipient bacterium produces a corresponding immunity protein. Using the model organism Burkholderia thailandensis, we show that delivery of a catalytically active CDI system toxin to immune (self) bacteria results in gene expression and phenotypic changes within the recipient cells. Termed contact-dependent signaling (CDS), this response promotes biofilm formation and other community-associated behaviors. Engineered strains that are isogenic with B. thailandensis, except the DNA region encoding the toxin and immunity proteins, did not display CDS, whereas a strain of Burkholderia dolosa producing a nearly identical toxin-immunity pair induced signaling in B. thailandensis. Our data indicate that bcpAIOB loci confer dual benefits; they direct antagonism toward non-self bacteria and promote cooperation between self bacteria, with self being defined by the bcpAIOB allele and not by genealogic relatedness.

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