title: "Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.
abstract: 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 commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximately 90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella 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 the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. 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.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814-4799, USA. maurelli@usuhsb.usuhs.mil
authors.forename: A T
authors.initials: AT
authors.lastname: Maurelli
authors.forename: R E
authors.initials: RE
authors.lastname: Fernández
authors.forename: C A
authors.initials: CA
authors.lastname: Bloch
authors.forename: C K
authors.initials: CK
authors.lastname: Rode
authors.forename: A
authors.initials: A
authors.lastname: Fasano
mesh_terms: D002103:Cadaverine; D002262:Carboxy-Lyases / Q000235:genetics; D004405:Dysentery, Bacillary / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology*; D017353:Gene Deletion; D016680:Genome, Bacterial; D006367:HeLa Cells; D006801:Humans; D012760:Shigella / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D002262:Carboxy-Lyases; C021520:lysine decarboxylase; D002103:Cadaverine