Abstract
BackgroundEffectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and therefore the identification of these effectors is important in understanding virulence. However, the effectors display high level of sequence diversity, therefore making the identification a difficult process. There is a need to collate and annotate existing effector sequences in public databases to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes that can be validated by a smaller number of key experiments.ResultsHerein, we present T3SEdb http://effectors.bic.nus.edu.sg/T3SEdb, a specialized database of annotated T3SS effector (T3SE) sequences containing 1089 records from 46 bacterial species compiled from the literature and public protein databases. Procedures have been defined for i) comprehensive annotation of experimental status of effectors, ii) submission and curation review of records by users of the database, and iii) the regular update of T3SEdb existing and new records. Keyword fielded and sequence searches (BLAST, regular expression) are supported for both experimentally verified and hypothetical T3SEs. More than 171 clusters of T3SEs were detected based on sequence identity comparisons (intra-cluster difference up to ~60%). Owing to this high level of sequence diversity of T3SEs, the T3SEdb provides a large number of experimentally known effector sequences with wide species representation for creation of effector predictors. We created a reliable effector prediction tool, integrated into the database, to demonstrate the application of the database for such endeavours.ConclusionsT3SEdb is the first specialised database reported for T3SS effectors, enriched with manual annotations that facilitated systematic construction of a reliable prediction model for identification of novel effectors. The T3SEdb represents a platform for inclusion of additional annotations of metadata for future developments of sophisticated effector prediction models for screening and selection of putative novel effectors from bacterial genomes/proteomes that can be validated by a small number of key experiments.
Highlights
Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and the identification of these effectors is important in understanding virulence
There is a need to collate and annotate these known effector sequences to enable systematic analyses of these sequences for development of models for screening and selection of putative novel effectors from bacterial genomes/proteomes that can be validated by a small number of key experiments
The experimental status of each record was defined following the comprehensive annotation procedure that we defined http://effectors. bic.nus.edu.sg/T3SEdb/annotationpolicy.php, which involved manually scanning through the literature via PubMed [8], cross-referencing functional annotations in corresponding records of the effectors in the UniProt/ Swiss-Prot database [9], and performing BLAST [10] search against the non-redundant sequences database
Summary
Effectors of Type III Secretion System (T3SS) play a pivotal role in establishing and maintaining pathogenicity in the host and the identification of these effectors is important in understanding virulence. The effectors display high level of sequence diversity, making the identification a difficult process. The Type III Secretion System (T3SS) is an essential mechanism for host-pathogen interaction during the infection process and is found in many gram-negative bacteria pathogens and eukaryotic cell symbionts [1]. Due to the key role of T3SE proteins in the establishment and maintenance of bacterial pathogenicity, there is considerable research interest in the identification of T3SS effectors. T3SEs display high level of sequence diversity, due largely to horizontal gene transfer among evolutionarily distant species and subsequent bacterial adaptation to different host cell environments [6]. While quite a number of T3SEs have been identified by both in vitro and in silico methods, the rising number of effector sequences being discovered each year suggests that this represents only a small proportion of all effectors, with many more yet to be discovered
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