Genomes of the Most Dangerous Epidemic Bacteria Have a Virulence Repertoire Characterized by Fewer Genes but More Toxin-Antitoxin Modules

Kalliopi Georgiades,Didier Raoult,Najib El-Sayed

doi:10.1371/journal.pone.0017962

Abstract

BackgroundWe conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. We also determined whether virulence is dictated by rules, or if it is the result of individual evolutionary histories. We systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans (“bad bugs”) to their closest non-epidemic related species (“controls”).Methodology/Principal FindingsWe found several significantly different features in the “bad bugs”, one of which was a smaller genome that likely resulted from a degraded recombination and repair system. The 10 Cluster of Orthologous Group (COG) functional categories revealed a significantly smaller number of genes in the “bad bugs”, which lacked mostly transcription, signal transduction mechanisms, cell motility, energy production and conversion, and metabolic and regulatory functions. A few genes were identified as virulence factors, including secretion system proteins. Five “bad bugs” showed a greater number of poly (A) tails compared to the controls, whereas an elevated number of poly (A) tails was found to be strongly correlated to a low GC% content. The “bad bugs” had fewer tandem repeat sequences compared to controls. Moreover, the results obtained from a principal component analysis (PCA) showed that the “bad bugs” had surprisingly more toxin-antitoxin modules than did the controls.Conclusions/SignificanceWe conclude that pathogenic capacity is not the result of “virulence factors” but is the outcome of a virulent gene repertoire resulting from reduced genome repertoires. Toxin-antitoxin systems could participate in the virulence repertoire, but they may have developed independently of selfish evolution.

Highlights

The virulence of pathogenic bacteria has been attributed to virulence factors, and pathogenic bacteria are considered to be better armed compared to bacteria that do not cause disease [1]
We looked for autotransporter proteins usually used by gram-negative bacteria to deliver large-size virulence factors and for iron uptake proteins [12]
We found that Y. pestis, B. pertussis, S. pneumoniae, S. dysenteriae and V. cholerae had more eukaryotic-like motifs than did their related control species

Summary

Introduction

The virulence of pathogenic bacteria has been attributed to virulence factors, and pathogenic bacteria are considered to be better armed compared to bacteria that do not cause disease [1]. In support of this hypothesis, the deletion of genes in pathogens has a detrimental effect on their fitness and on their ability to cause diseases [2]. Genes that encode ‘‘virulence factors’’ are found in the genomes of non-pathogenic bacteria [11,12], such as free-living bacteria, which may carry more ‘‘virulence factors’’ than do pathogenic bacteria. We conducted a comparative genomic study based on a neutral approach to identify genome specificities associated with the virulence capacity of pathogenic bacteria. We systematically compared the genomes of the 12 most dangerous pandemic bacteria for humans (‘‘bad bugs’’) to their closest non-epidemic related species (‘‘controls’’)

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Conclusion