Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomicsReport as inadecuate




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Biology Direct

, 7:18

First Online: 25 June 2012Received: 20 March 2012Accepted: 31 May 2012DOI: 10.1186-1745-6150-7-18

Cite this article as: Zhang, D., de Souza, R.F., Anantharaman, V.
et al.
Biol Direct 2012 7: 18.
doi:10.1186-1745-6150-7-18

Abstract

BackgroundProteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts.
These include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflicts.
They are characterized by a remarkable diversity of C-terminal toxin domains generated by recombination with standalone toxin-coding cassettes.
Prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules.
We systematically investigated polymorphic toxin systems using comparative genomics, sequence and structure analysis.

ResultsPolymorphic toxin systems are distributed across all major bacterial lineages and are delivered by at least eight distinct secretory systems.
In addition to type-II, these include type-V, VI, VII ESX, and the poorly characterized -Photorhabdus virulence cassettes PVC-, PrsW-dependent and MuF phage-capsid-like systems.
We present evidence that trafficking of these toxins is often accompanied by autoproteolytic processing catalyzed by HINT, ZU5, PrsW, caspase-like, papain-like, and a novel metallopeptidase associated with the PVC system.
We identified over 150 distinct toxin domains in these systems.
These span an extraordinary catalytic spectrum to include 23 distinct clades of peptidases, numerous previously unrecognized versions of nucleases and deaminases, ADP-ribosyltransferases, ADP ribosyl cyclases, RelA-SpoT-like nucleotidyltransferases, glycosyltranferases and other enzymes predicted to modify lipids and carbohydrates, and a pore-forming toxin domain.
Several of these toxin domains are shared with host-directed effectors of pathogenic bacteria.
Over 90 families of immunity proteins might neutralize anywhere between a single to at least 27 distinct types of toxin domains.
In some organisms multiple tandem immunity genes or immunity protein domains are organized into polyimmunity loci or polyimmunity proteins.
Gene-neighborhood-analysis of polymorphic toxin systems predicts the presence of novel trafficking-related components, and also the organizational logic that allows toxin diversification through recombination.
Domain architecture and protein-length analysis revealed that these toxins might be deployed as secreted factors, through directed injection, or via inter-cellular contact facilitated by filamentous structures formed by RHS-YD, filamentous hemagglutinin and other repeats.
Phyletic pattern and life-style analysis indicate that polymorphic toxins and polyimmunity loci participate in cooperative behavior and facultative ‘cheating’ in several ecosystems such as the human oral cavity and soil.
Multiple domains from these systems have also been repeatedly transferred to eukaryotes and their viruses, such as the nucleo-cytoplasmic large DNA viruses.

ConclusionsAlong with a comprehensive inventory of toxins and immunity proteins, we present several testable predictions regarding active sites and catalytic mechanisms of toxins, their processing and trafficking and their role in intra-specific and inter-specific interactions between bacteria.
These systems provide insights regarding the emergence of key systems at different points in eukaryotic evolution, such as ADP ribosylation, interaction of myosin VI with cargo proteins, mediation of apoptosis, hyphal heteroincompatibility, hedgehog signaling, arthropod toxins, cell-cell interaction molecules like teneurins and different signaling messengers.

ReviewersThis article was reviewed by AM, FE and IZ.

Electronic supplementary materialThe online version of this article doi:10.1186-1745-6150-7-18 contains supplementary material, which is available to authorized users.

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Author: Dapeng Zhang - Robson F de Souza - Vivek Anantharaman - Lakshminarayan M Iyer - L Aravind

Source: https://link.springer.com/



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