Pathoadaptive mutations that enhance virulence: Genetic organization of the cadA regions of Shigella spp.

Pathoadaptive mutations improve the fitness of pathogenic species by modifi cation of traits that interfere with factors (virulence and ancestral) requ ired for survival in host tissues. A demonstrated pathoadaptive mutation is the loss of lysine decarboxylase (LDC) expression in Shigella species that have evolved from LDC-expressing Escherichia coli. Previous studies demons trated that the product of LDC activity, cadaverine, blocks the action of S higella enterotoxins and that the gene encoding LDC, cadA, was abolished by large chromosomal deletions In each Shigella species. To better understand the nature and evolution of these pathoadaptive mutations, remnants of the cad region were sequenced from the four Shigella species. These analyses r eveal novel gene arrangements in this region of tile pathogens' chromosomes . Insertion sequences, a phage genome, and/or loci from different positions on the ancestral E. coli chromosome displaced the cadA locus to form disti nct genetic linkages that are unique to each Shigella species. Hybridizatio n studies, using an E. coli K-12 microarray, indicated that the genes displ aced to form the novel linkages still remain in the Shigella genomes. None of these novel gene arrangements were observed in representatives of all E. coli phylogenies. Collectively, these observations indicate that inactivat ion of the cadA antivirulence gene occurred independently in each Shigella species. The convergent evolution of these pathoadaptive mutations demonstr ates that, following evolution from commensal E. coli, strong pressures in host tissues selected Shigella clones with increased fitness and virulence through the loss of an ancestral trait (LDC). These observations strongly s upport tile role of pathoadaptive mutation as an important pathway in the e volution of pathogenic organisms.