scholarly journals Class II Contact-Dependent growth Inhibition (CDI) systems allow for broad-range cross-species toxin delivery

2019 ◽  
Author(s):  
Petra Virtanen ◽  
Marcus Wäneskog ◽  
Sanna Koskiniemi
Keyword(s):  
Growth Inhibition ◽  
Receptor Binding ◽  
Class Ii ◽  
Receptor Protein ◽  
Bacterial Populations ◽  
Cognate Receptor ◽  
Binding Domains ◽  
Dependent Growth ◽  
Species Specific ◽  
Contact Dependent Growth Inhibition

AbstractContact-dependent growth inhibition (CDI) allows bacteria to recognize kin cells in mixed bacterial populations. In Escherichia coli, CDI mediated effector delivery has been shown to be species-specific, with a preference for the own strain over others. This specificity is achieved through an interaction between a receptor-binding domain in the CdiA protein and its cognate receptor protein on the target cell. But how conserved this specificity is has not previously been investigated in detail. Here we show that three different class II CdiA receptor-binding domains and their Enterobacter cloacae analog are highly promiscuous, allowing for efficient effector delivery into several different Enterobacteriaceae species, including Escherichia, Enterobacter, Klebsiella and Salmonella spp. In addition, although we observe a preference for some receptors over others, this did not limit cross-species effector delivery, suggesting that class II CdiA proteins can allow for broad-range and cross-species growth inhibition in mixed bacterial populations.

scholarly journals Contact-Dependent Growth Inhibition in Bacteria: Do Not Get Too Close!

2020 ◽  
Vol 21 (21) ◽  
pp. 7990
Author(s):  
Larisa N. Ikryannikova ◽  
Leonid K. Kurbatov ◽  
Neonila V. Gorokhovets ◽  
Andrey A. Zamyatnin
Keyword(s):  
Signal Transduction ◽  
Growth Inhibition ◽  
Physical Contact ◽  
Ecological Niches ◽  
Competitive Advantages ◽  
Interspecies Interactions ◽  
Human Pathogens ◽  
Bacterial Populations ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

Over millions of years of evolution, bacteria have developed complex strategies for intra-and interspecies interactions and competition for ecological niches and resources. Contact-dependent growth inhibition systems (CDI) are designed to realize a direct physical contact of one bacterial cell with other cells in proximity via receptor-mediated toxin delivery. These systems are found in many microorganisms including clinically important human pathogens. The main purpose of these systems is to provide competitive advantages for the growth of the population. In addition, non-competitive roles for CDI toxin delivery systems including interbacterial signal transduction and mediators of bacterial collaboration have been suggested. In this review, our goal was to systematize the recent findings on the structure, mechanisms, and purpose of CDI systems in bacterial populations and discuss the potential biological and evolutionary impact of CDI-mediated interbacterial competition and/or cooperation.

scholarly journals Contact‐dependent growth inhibition induces high levels of antibiotic‐tolerant persister cells in clonal bacterial populations

2018 ◽  
Vol 37 (9) ◽  
Author(s):  
Anirban Ghosh ◽  
Özden Baltekin ◽  
Marcus Wäneskog ◽  
Dina Elkhalifa ◽  
Disa L Hammarlöf ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Persister Cells ◽  
Bacterial Populations ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

scholarly journals CdiA Effectors Use Modular Receptor-Binding Domains To Recognize Target Bacteria

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Zachary C. Ruhe ◽  
Josephine Y. Nguyen ◽  
Jing Xiong ◽  
Sanna Koskiniemi ◽  
Christina M. Beck ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Central Region ◽  
Genetic Recombination ◽  
Receptor Binding Domain ◽  
Receptor Specificity ◽  
E Coli ◽  
Binding Domains ◽  
Specific Receptors ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

ABSTRACT Contact-dependent growth inhibition (CDI) systems encode CdiA effectors, which bind to specific receptors on neighboring bacteria and deliver C-terminal toxin domains to suppress target cell growth. Two classes of CdiA effectors that bind distinct cell surface receptors have been identified, but the molecular basis of receptor specificity is not understood. Alignment of BamA-specific CdiA EC93 from Escherichia coli EC93 and OmpC-specific CdiA EC536 from E. coli 536 suggests that the receptor-binding domain resides within a central region that varies between the two effectors. In support of this hypothesis, we find that CdiA EC93 fragments containing residues Arg1358 to Phe1646 bind specifically to purified BamA. Moreover, chimeric CdiA EC93 that carries the corresponding sequence from CdiA EC536 is endowed with OmpC-binding activity, demonstrating that this region dictates receptor specificity. A survey of E. coli CdiA proteins reveals two additional effector classes, which presumably recognize distinct receptors. Using a genetic approach, we identify the outer membrane nucleoside transporter Tsx as the receptor for a third class of CdiA effectors. Thus, CDI systems exploit multiple outer membrane proteins to identify and engage target cells. These results underscore the modularity of CdiA proteins and suggest that novel effectors can be constructed through genetic recombination to interchange different receptor-binding domains and toxic payloads. IMPORTANCE CdiB/CdiA two-partner secretion proteins mediate interbacterial competition through the delivery of polymorphic toxin domains. This process, known as contact-dependent growth inhibition (CDI), requires stable interactions between the CdiA effector protein and specific receptors on the surface of target bacteria. Here, we localize the receptor-binding domain to the central region of E. coli CdiA. Receptor-binding domains vary between CdiA proteins, and E. coli strains collectively encode at least four distinct effector classes. Further, we show that receptor specificity can be altered by exchanging receptor-binding regions, demonstrating the modularity of this domain. We propose that novel CdiA effectors are naturally generated through genetic recombination to interchange different receptor-binding domains and toxin payloads.

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 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
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