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Infection and Immunity, December 2001, p. 7471-7480, Vol. 69, No. 12
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.12.7471-7480.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Pathoadaptive Mutations That Enhance Virulence:
Genetic Organization of the cadA Regions of
Shigella spp.
William A.
Day Jr.,
Reinaldo E.
Fernández, and
Anthony T.
Maurelli*
Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services
University of the Health Sciences, Bethesda, Maryland 20814-4799
Received 5 June 2001/Returned for modification 12 July
2001/Accepted 29 August 2001
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.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, F. Edward Hébert School of Medicine,
Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814-4799. Phone: (301) 295-3415. Fax: (301) 295-1545. E-mail: amaurelli{at}usuhs.mil.
Infection and Immunity, December 2001, p. 7471-7480, Vol. 69, No. 12
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.12.7471-7480.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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