Pathogenicity Islands: Bacterial Evolution in Quantum Leaps

Abstract

“I am the beneficiary of a lucky break in the genetic sweepstakes” Isaac Asimov For most bacterial pathogens virulence is a multifactorial process requiring two general classes of determinants. The first encompasses genes that participate in physiological processes necessary for survival in host and non-host environments, and these genes are generally found in both pathogenic and non-pathogenic organisms. In Salmonella, this set includes regulatory genes, such as phoP/phoQ, that control expression of more than 20 loci in response to low magnesium environments; biosynthetic genes, such as aroA, that encodes the ability to synthesize aromatic amino acids not found in host tissues; and several additional genes required for cell maintenance and DNA repair (9Groisman E.A Ochman H Trends Microbiol. 1994; 2: 289-294Abstract Full Text PDF PubMed Scopus (46) Google Scholar). The second class of virulence genes specifies traits that are unique to pathogens, and, not surprisingly, these genes are rarely detected in non-pathogenic organisms. Based on the initial characterizations of plasmids from Yersinia and Shigella, such sequences were originally thought to be confined to extrachromosomal elements; but recently, several virulence cassettes have been mapped to the chromosome of pathogenic organisms. These segments of the chromosome, termed pathogenicity islands (11Hacker J Bender L Ott M Wingender J Lund B Marre R Goebel W Microb. Pathogen. 1990; 8: 213-225Crossref PubMed Scopus (209) Google Scholar, 13Lee C.A Infect. Agents Dis. 1996; 5: 1-7PubMed Google Scholar; see Figure 1), can be of any length, but, most often, they accommodate large clusters of genes contributing a particular virulence phenotype. Pathogenicity islands have been recognized by their association with transmissible DNA, their sporadic distribution in a set of related pathogenic and non-pathogenic organisms, or the unusual features of their encoded genes, and their recent characterization has provided clues regarding their origins, distribution, mode of transfer, and genetic stability. Incorporation of a pathogenicity island can, in a single step, transform a normally benign organism into a pathogen. For example, enteropathogenic E. coli contain a chromosomal segment that mediates attaching and effacing lesions on intestinal epithelial cells (14McDaniel T.K Jarvis K.G Donnenberg M.S Kaper J.B Proc. Natl. Acad. Sci. USA. 1995; 92: 1664-1668Crossref PubMed Scopus (996) Google Scholar; Figure 1). This 35 kb region—termed LEE for locus of enterocyte effacement—is absent from laboratory strains and codes for an outer membrane protein that promotes contact with host cells and a type III secretion system that exports proteins known to modify host cell functions. Type III secretion systems are prevalent among animal and plant pathogens—homologous export systems are responsible for the secretion of virulence proteins by Yersinia, Erwinia, Pseudomonas, Xanthomonas, Shigella, and Salmonella (18Van Gijsegem F Genin S Boucher C Trends Microbiol. 1993; 1: 175-180Abstract Full Text PDF PubMed Scopus (171) Google Scholar)—and these systems differ from the sec-dependent pathway in that their effector molecules lack a typical signal sequence. At the same location where LEE has inserted into enteropathogenic strains (14McDaniel T.K Jarvis K.G Donnenberg M.S Kaper J.B Proc. Natl. Acad. Sci. USA. 1995; 92: 1664-1668Crossref PubMed Scopus (996) Google Scholar) a distinct pathogenicity island, PAI-1, has been identified in a uropathogenic strain of E. coli (2Blum G Ott M Lischewski A Ritter A Imrich H Tschäpe H Hacker J Infect. Immun. 1994; 62: 606-614PubMed Google Scholar; Figure 1). Both islands are targeted to the same basepair downstream of the selC gene, which codes for the selenocysteine-specific tRNA. LEE and PAI-1 contain different sets of genes: PAI-1 is 70 kb in length and encodes a hemolysin. Thus, the specific cassette incorporated at the selC locus determines whether strains of E. coli are converted into entero- or uropathogens. Aside from PAI-1 and LEE, three other pathogenicity islands have been identified in E. coli (Figure 1); and, in fact, certain uropathogenic strains contain more than one pathogenicity island. In addition to PAI-1, E. coli strain 536 also harbors a 190-kb pathogenicity island, PAI-2, that has integrated at the tRNAleuX locus and contains genes for an alternate hemolysin and Prf-type fimbriae (2Blum G Ott M Lischewski A Ritter A Imrich H Tschäpe H Hacker J Infect. Immun. 1994; 62: 606-614PubMed Google Scholar). The other pathogenicity islands detected in E. coli also contain hemolysin genes but are associated with different tRNA loci: the island at the pheV locus contains genes for P-fimbriae, which allow the pathogen to adhere to cells lining the urinary tract, whereas the island at the pheR locus codes for Prs fimbriae, which bind Gal Nac-1–3-Gal Nac–containing receptors rather the Gal-β-1–4-Gal residues recognized by the P fimbrial