Abstract
Bacterial pathogens have evolved numerous strategies to corrupt, hijack or mimic cellular processes in order to survive and proliferate. Among those strategies, Type IV effectors (T4Es) are proteins secreted by pathogenic bacteria to manipulate host cell processes during infection. They are delivered into eukaryotic cells in an ATP-dependent manner via the type IV secretion system, a specialized multiprotein complex. T4Es contain a wide spectrum of features including eukaryotic-like domains, localization signals or a C-terminal translocation signal. A combination of these features enables prediction of T4Es in a given bacterial genome. In this study, we developed a web-based comprehensive suite of tools with a user-friendly graphical interface. This version 2.0 of S4TE (Searching Algorithm for Type IV Effector Proteins; http://sate.cirad.fr) enables accurate prediction and comparison of T4Es. Search parameters and threshold can be customized by the user to work with any genome sequence, whether publicly available or not. Applications range from characterizing effector features and identifying potential T4Es to analyzing the effectors based on the genome G+C composition and local gene density. S4TE 2.0 allows the comparison of putative T4E repertoires of up to four bacterial strains at the same time. The software identifies T4E orthologs among strains and provides a Venn diagram and lists of genes for each intersection. New interactive features offer the best visualization of the location of candidate T4Es and hyperlinks to NCBI and Pfam databases. S4TE 2.0 is designed to evolve rapidly with the publication of new experimentally validated T4Es, which will reinforce the predictive power of the algorithm. The computational methodology can be used to identify a wide spectrum of candidate bacterial effectors that lack sequence conservation but have similar amino acid characteristics. This approach will provide very valuable information about bacterial host-specificity and virulence factors and help identify host targets for the development of new anti-bacterial molecules.
Highlights
Proteobacteria have evolved specific effector proteins to manipulate host cell gene expression and processes, hijack immune responses and exploit host cell machinery during infection
Bacterial EPIYA effectors are delivered into host cells by T4SS, where they undergo tyrosine phosphorylation at the EPIYA motif and thereby manipulate host signalling by tight interaction with SH2 domain-containing proteins [11]
We searched for conserved EPIYA motifs (EPIYA, ENIYE, NPLYE, EHLYA, TPLYA, EPLYA, ESIYE, EDLYA, EPIYG, EPVYA, VPNYA, EHIYD) in different bacteria that have a type IV secretion system and we searched for hypothetical EPIYA motifs using the motif E-X-X-Y-X
Summary
Proteobacteria have evolved specific effector proteins to manipulate host cell gene expression and processes, hijack immune responses and exploit host cell machinery during infection. S4TE 2.0 is a tool for in silico screening of proteobacteria genomes and T4E prediction based on the combined use of 14 distinctive features. In this updated version, modules searching for promoter motifs, homology, NLS, MLS and E-block are more efficient. S4TE 2.0 offers advanced users an expert mode (S4TE-EM) they can use to customize S4TE 2.0 search parameters (e.g. exclude modules, modify module weightings) In this mode, S4TE 2.0 can be used as 14 independent programs to search for particular features in a given bacterial genome (e.g. NLS, C-ter charges). All S4TE 2.0 results are interactive and linked to NCBI and Pfam databases
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