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Table 1 Features of secretion pathways by which polymorphic toxins are exported

From: Polymorphic toxin systems: Comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics

Secretion pathway

Signature N-terminal leader domains or pre-toxin-domains

Signature genes in neighborhood

Processing proteases/repeats in toxin proteins

Phyletic patterns

Additional Notes

T2SS/Sec-dependent system

Signal peptide

-

Proteases: Caspase, HINT, MCF1-SHE, subtilisin3, ZU54

In all bacteria

Default pathway for protein export. Might contain MAFB-N (DUF1020), MicroscillaN, APD1, APD2, Inactive transglutaminase

   

Repeats: ALF, ankyrins, β-propeller, RHS, Sel11, TPR1, Tail-fiber2

  

T5SS

N-terminal TpsA-like secretion domain (TPSASD)

FhaB/CdiB coding for porin-like protein

Proteases: HINT Repeats: FilH

α,β,γ,δ,ϵ-proteobacteria, acidobacteria, bacteroidetes/chlorobi, firmicutes5, fusobacteria

The TPSASD domain binds the outer-membrane FhaB/CdiB during the export of the toxin domain

 

Pre-toxin domains: DUF637(PT637),DUF637-N, PT-VENN

    

T6SS

VgrG domain, PAAR domain, Hcp1

ClpV-like AAA + Atpase, MOG1/PspB-like, VgrG, Hcp1, Phage tail/base-plate related proteins

Repeats: RHS

All proteobacteria, acidobacteria, bacteroidetes/chlorobi, firmicutes

Complete T6SS delivered toxins are often typified by a N-terminal PAAR domain

Photorhabdus virulence cassette pathway (PVC)

PVC-Metallopeptidase

CDC48-like AAA + ATPase, VgrG, Phage tail/base-plate related proteins

Proteases: Metallopeptidase, Subtilisin, Caspase, MCF1-SHE

Euryarchaeota, α,β,γ,δ,ϵ-proteobacteria, acidobacteria, actinobacteria, bacteroidetes, chlorobi, chloroflexi, cyanobacteria, deinococci, firmicutes, nitrospirae, spirochaetes

 
   

Repeats: RHS, tail fiber

  

T7SS/ESX/ESAT-6 secretion system

WxG, LxG, LDxD domains

YueA-like FtsK/HerA ATPase, EsaC

Proteases: HINT, Caspase, MCF1-SHE Repeats: RHS, Tail-fiber

Firmicutes, actinobacteria, chloroflexi, other bacterial lineages6

Toxins exported by these systems may or may not possess repeat domains

TcdB/TcaC

A signal peptide followed by a SpvB domain coupled to a C-terminal integrin-like β-propeller domain

TcdB

Repeats : Integrin-like beta propeller, RHS, tail-fiber

Euryarchaeota, α,β,γ,δ-proteobacteria, actinobacteria, bacteroidetes

 
    

Chloroflexi, fibrobacteres, firmicutes, lentisphaerae, spirochaetes

 
   

Proteases: HINT, Caspase, ZU5

  

PrsW

PrsW-peptidase domain

 

Repeats: RHS

Euryarchaeota, α,β,γ,δ-proteobacteria, actinobacteria Bacteroidetes, chloroflexi, cyanobacteria,deinococci, dictyoglomi, firmicutes, fusobacteria, gemmatimonadetes, spirochaetes, verrucomicrobia

PrsW is a transmembrane peptidase with several transmembrane helices

   

Proteases: PrsW

  

Phage DNA packaging system

MuF

MuF, large and small subunits of terminase

Proteases: Papain-like

Euryarchaeota, acidobacteria, α,γ,δ-proteobacteria, actinobacteria, bacteroidetes, chlorobi, firmicutes, fusobacteria, spirochaetes, caudovirales

The toxin is predicted to be packaged into the phage head as in phage transduction systems

  1. 1: Note only fused to toxins exported by the SEC-dependent pathway in Amoebophilus asiaticus; 2. Note only fused to toxins exported by the SEC-dependent pathway in Microscilla marina; 3: Note only fused to toxins exported by the SEC-dependent pathway in Acetivibrio cellulolyticus; 4: Note only fused to toxins exported by the SEC-dependent pathway in Caldicellulosiruptor species; 5: Note in firmicutes, the export pathway is only present in Veillonella and Selenomonas species, also referred to as the Negativicutes species; 6: Certain bacterial lineages within the β,ϵ,γ-proteobacteria, planctomycetes, verrucomicrobia, cyanobacteria and bacteroidetes have solo WXG domains that have a distinct YueA-like ATPase with 3 HerA/FtsK domains of which only the middle one is active. These appear to be mobile versions of T7SS.