“Black holes” and bacterial pathogenicity: A large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example,Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensalEscherichia coli in the presence of a plasmid inShigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in ≈90% ofE. coli strains but is uniformly absent inShigella strains. When the gene for LDC,cadA , was introduced intoShigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of theS. flexneri 2a and laboratoryE. coli K-12 genomes in the region ofcadA revealed a large deletion inShigella . Representative strains ofShigella spp. and enteroinvasiveE. coli displayed similar deletions ofcadA . Our results suggest that, asShigella spp. evolved fromE. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these “black holes,” deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.