Pathogenicity islands: bacterial evolution in quantum leaps.

Is the acquisition of a pathogenicity island sufficient to transform an organism into a pathogen? Three factors determine the virulence role of pathogenicity islands: the genes within the island, the status of the recipient microorganism, and features of the host that promote the progression of disease. The incorporation of certain genes, such as those encoding cholera toxin, would be sufficient to convert any organism into a pathogen because administration of the toxin itself is sufficient to produce the symptoms of the disease. But for most other cases, the utility of sequences obtained through gene transfer varies with the organism. E. coli is a benign constituent of the mammalian intestinal flora and is apparently predisposed to become a pathogen by the introduction of several types of virulence genes. The LEE island is likely to encode all of the genes necessary to produce attachment and effacement lesions, and the acquisition of this island could probably render any strain of E. coli pathogenic. And, not surprisingly, pathogenicity islands causing these lesions have been detected in genetically diversed strains of E. coli.The acquisition of pathogenicity islands offers a rapid method of evolving novel functions; however, the introgressed sequences, even when they encode their specific regulators as part of complete functional units, must interact with rest of the genome. Expression of six invasion genes within the SPI-1 island of Salmonella is governed by the PhoP/PhoQ regulatory system (Galan 1996xGalan, J.E. Mol. Microbiol. 1996; 20: 263–272Crossref | PubMed | Scopus (329)See all ReferencesGalan 1996), which is not encoded within the SPI-1 island and is present in both pathogenic and non-pathogenic microorganisms. And even sequences that are maintained on extrachromosomal elements can be regulated by chromosomal loci: the invasion genes on the Shigella virulence plasmid are controlled by the chromosomally-encoded histone-like protein H1.The association of pathogenicity islands with mobile DNA elements suggests that these sequences could be incorporated into a wide variety of bacterial species. However, presence of a pathogenicity island does not assure the transformation of an organism into a pathogen. A 10 kb region that harbors most known virulence genes in the pathogenic species of Listeria (L. monocytogenes and L. ivanovii) is also present in the chromosome of the nonpathogenic L. seeligeri (Gouin et al. 1994xGouin, E, Mengaud, J, and Cossart, P. Infect. Immun. 1994; 62: 3550–3553PubMedSee all ReferencesGouin et al. 1994). While this gene cluster also encodes a pleiotropic activator, the attenuated phenotype of L. seeligeri has been ascribed to down regulation of most virulence genes. Furthermore, due to the coevolution between microbes and their hosts, the virulence potential of pathogenicity islands will only manifest in suitable animals and plants.Finally, it has been suggested that the deletion of pathogenicity islands may represent a regulatory mechanism to control expression of virulence genes (Blum et al. 1994xBlum, G, Ott, M, Lischewski, A, Ritter, A, Imrich, H, Tschape, H, and Hacker, J. Infect. Immun. 1994; 62: 606–614PubMedSee all ReferencesBlum et al. 1994). This presupposes that the elimination of pathogenicity islands will circumvent the immune response to the encoded determinants and allow rapid microbial replication by reducing chromosome size. While this is a plausible scenario, both pathogenic and non-pathogenic strains of E. coli contain surface antigens that can promote an immune response, and the growth rates of natural strains of E. coli under lab conditions are not associated with genome size. Therefore, the deletion of pathogenicity islands is probably not a mechanism employed by bacteria to modulate virulence, but simply reflects the intrinsic genetic instability of these sequences.