Abstract

BackgroundPathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs.ResultsWe present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s) of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs.ConclusionSupporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s) and origin(s) of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic genomes will broaden our knowledge on the structure and properties of PAIs and the evolution of bacterial pathogenesis.

Highlights

  • Pathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event

  • PAI-like regions When every ORF contained in 207 PAI loci were similarity-searched against the ORFs present in the 148 prokaryotic genomes, 1,490 genomic strips of PAI-associated genes were defined based on the proximity of the homologs of genes from the same PAI accession

  • The plot indicates that clusters of PAI-homologs are often located in the backbone sequence while the detected GIs tend to be biased to have lower G+C content

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Summary

Introduction

Pathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage These approaches often lead to the identification of genomic islands, rather than PAIs. PAIs are distinct genetic elements of pathogens encoding various virulence factors such as protein secretion systems, host invasion factors, iron uptake systems, and toxins [1,2]. Compositional approaches may generate many false positives due to other factors such as selection and mutation bias [8,9], and a lot of false negatives owing to adjustment of the transferred sequence in its composition by amelioration [10] These methods detect different sets of ORFs as foreign origin when applied to the genome of Escherichia coli K-12 [11].

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