scholarly journals Burkholderia multivorans requires species‐specific GltJK for entry of a contact‐dependent growth inhibition system protein

2021 ◽  
Author(s):  
Tanya Myers‐Morales ◽  
Martha M.S. Sim ◽  
Tanner J. DuCote ◽  
Erin C. Garcia
Keyword(s):  
Growth Inhibition ◽  
Burkholderia Multivorans ◽  
Dependent Growth ◽  
Species Specific ◽  
Contact Dependent Growth Inhibition

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 Burkholderia cepacia Complex Contact-Dependent Growth Inhibition Systems Mediate Interbacterial Competition

2019 ◽  
Vol 201 (12) ◽  
Author(s):  
Tanya Myers-Morales ◽  
A. Elizabeth Oates ◽  
Matthew S. Byrd ◽  
Erin C. Garcia
Keyword(s):  
Cystic Fibrosis ◽  
Growth Inhibition ◽  
Burkholderia Cepacia ◽  
Gram Negative Bacteria ◽  
Immunity Protein ◽  
Gram Negative ◽  
Content Type ◽  
Burkholderia Multivorans ◽  
Dependent Growth ◽  
Contact Dependent Growth Inhibition

ABSTRACT Burkholderia species, including opportunistic pathogens in the Burkholderia cepacia complex (Bcc), have genes to produce contact-dependent growth inhibition (CDI) system proteins. CDI is a phenomenon in which Gram-negative bacteria use the toxic C terminus of a polymorphic surface-exposed exoprotein, BcpA, to inhibit the growth of susceptible bacteria upon direct cell-cell contact. Production of a small immunity protein, BcpI, prevents autoinhibition. Although CDI systems appear widespread in Gram-negative bacteria, their function has been primarily examined in several model species. Here we demonstrate that genes encoding predicted CDI systems in Bcc species exhibit considerable diversity. We also show that Burkholderia multivorans, which causes pulmonary infections in patients with cystic fibrosis, expresses genes that encode two CDI systems, both of which appear distinct from the typical Burkholderia-type CDI system. Each system can mediate intrastrain interbacterial competition and contributes to bacterial adherence. Surprisingly, the immunity-protein-encoding bcpI gene of CDI system 1 could be mutated without obvious deleterious effects. We also show that nonpathogenic Burkholderia thailandensis uses CDI to control B. multivorans growth during coculture, providing one of the first examples of interspecies CDI and suggesting that CDI systems could be manipulated to develop therapeutic strategies targeting Bcc pathogens. IMPORTANCE Competition among bacteria affects microbial colonization of environmental niches and host organisms, particularly during polymicrobial infections. The Bcc is a group of environmental bacteria that can cause life-threatening opportunistic infections in patients who have cystic fibrosis or are immunocompromised. Understanding the mechanisms used by these bacterial pathogens to compete with one another may lead to the development of more effective therapies. Findings presented here demonstrate that a Bcc species, Burkholderia multivorans, produces functional CDI system proteins and that growth of this pathogen can be controlled by CDI system proteins produced by neighboring Burkholderia cells.

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

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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