Genomes of the most dangerous epidemic bacteria have a virulence repertoire characterized by fewer genes but more toxin-antitoxin modules

Abstract

Background: We 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 findings: We 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/significance: We 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.

Figure 1. Principal Component Analysis of 11 genomic characteristics.

A. Toxin-antitoxin systems (TA) characterize “bad bugs”. B. Bacterial character (“bad bugs”/controls) according to the TA content. The red dots representing the “bad bugs” are positioned separately from the blue dots representing the controls.

Figure 2. Recombination and repair genes.

The “bad bugs” lack recombinational repair genes, whereas the controls lack mismatch excision repair genes.

Figure 3. Hyperspecialized pathogenic species evolution.

The circles with various colors represent different bacteria; the small brown circles represent the gene repertoire; the arrows around the bacteria represent gene exchange; the leaf, mouth and lungs represent the different potential niches colonized by a species. The red circle is a hyperspecialized bacterium with a decreased gene repertoire via gene loss.