The continuing evolution of a bacterial pathogen.

A lthough Escherichia coli is a prototypic commensal bacterial species of the mammalian intestine and a laboratory workhorse for molecular biology, certain strains of this species are capable of causing significant human disease. The spectrum of disease caused by E. coli includes enteric/diarrheal disease, urinary tract infections, renal failure, and sepsis/meningitis (1). The different pathotypes of E. coli possess genes encoding a wide variety of virulence factors that are frequently encoded on mobile genetic elements such as bacteriophages, plasmids, and pathogenicity islands. E. coli strains can be serotyped as one of 10,000 possible combinations of O (LPS) and H (flagellar) antigens, but one serotype, O157:H7, has achieved particular notoriety as a cause of deadly outbreaks of food-borne illness throughout the world. The work of Manning et al. (2) in this issue of PNAS reveals significant new information on the evolution and genetic composition of E. coli strains belonging to the O157:H7 serotype and reports the emergence of a new variant that appears to cause more severe disease. First recognized a quarter of a century ago, E. coli O157:H7 causes bloody and nonbloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS), which is the leading cause of acute renal failure in children. One of the most potent toxins ever described, Shiga toxin, is a critical virulence factor in HUS, and different variants of this bacteriophage-encoded toxin, e.g., Stx1, Stx2, Stx2c, are found in this pathogen. The mechanism of Shiga toxin is similar to that of ricin and involves inhibition of protein synthesis in renal endothelial and other cells. Toxin produced in the intestine enters the circulation, resulting in direct and indirect effects on the kidney. Other important virulence factors include the type III secretion system encoded on the locus of enterocyte effacement (LEE) pathogenicity island and a variety of secreted effector proteins encoded in the LEE and elsewhere in the genome. Previous work from the Whittam laboratory (3) indicates that E. coli O157:H7 evolved from enteropathogenic E. coli serotype O55:H7, a cause of nonbloody diarrhea, in a stepwise manner through the sequential acquisition of phage-encoded Stx2, a large virulence plasmid, an rfb locus that converted the somatic O antigen from O55 to O157, and additional chromosomal mutations. Comparative genomic studies of several E. coli O157:H7 strains have revealed extensive genomic diversity related to the structure, position, and genetic content of bacteriophages and variability in the content of putative virulence genes, including those encoding adhesins, Shiga toxins, and non-LEE effector proteins. These developments have led Wick et al. (3) to conclude that ‘‘O157:H7 genomes are rapidly diverging and radiating into new niches as the pathogen disseminates.’’