Affiliation:
1. Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799
Abstract
ABSTRACT
Pathoadaptive mutations improve the fitness of pathogenic species by modification of traits that interfere with factors (virulence and ancestral) required 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 demonstrated that the product of LDC activity, cadaverine, blocks the action of
Shigella
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 reveal novel gene arrangements in this region of the 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 distinct genetic linkages that are unique to each
Shigella
species. Hybridization studies, using an
E. coli
K-12 microarray, indicated that the genes displaced 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 inactivation of the
cadA
antivirulence gene occurred independently in each
Shigella
species. The convergent evolution of these pathoadaptive mutations demonstrates 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 support the role of pathoadaptive mutation as an important pathway in the evolution of pathogenic organisms.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
122 articles.
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