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 additi ons that contribute to the evolution of bacterial pathogens, For examp le, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence o f a plasmid in Shigella that encodes virulence functions, However, pat hogenic bacteria also may lack properties that are characteristic of n onpathogens. Lysine decarboxylase (LDC) activity is present in approxi mate to 90% of E. coli strains but is uniformly absent in Shigella str ains, When the gene for LDC, cadA, was introduced into Shigella flexne ri 2a, virulence became attenuated, and enterotoxin activity was inhib ited greatly, The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC, Comparison of the S. flexn eri 2a and laboratory E. coli K-12 genomes in the region of cadA revea led a large deletion in Shigella, Representative strains of Shigella s pp. and enteroinvasive E. coli displayed similar deletions of cadA, Ou r results suggest that, as Shigella spp. evolved from E. coli to becom e pathogens, they not only acquired virulence genes on a plasmid but a lso shed genes via deletions, The formation of these ''black holes,'' deletions of genes that are detrimental to a pathogenic lifestyle, pro vides an evolutionary pathway that enables a pathogen to enhance virul ence, Furthermore, the demonstration that cadaverine can inhibit enter otoxin activity may lead to more general models about toxin activity o r 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.