Dataset Information

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.

ABSTRACT: Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximately 90% of E. coli strains but is uniformly absent in Shigella strains. When the gene for LDC, cadA, was introduced into Shigella flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E. coli K-12 genomes in the region of cadA revealed a large deletion in Shigella. Representative strains of Shigella spp. and enteroinvasive E. coli displayed similar deletions of cadA. Our results suggest that, as Shigella spp. evolved from E. coli to become pathogens, they not only acquired virulence genes on a plasmid but also shed genes via deletions. The formation of these "black holes," deletions of genes that are detrimental to a pathogenic lifestyle, provides an evolutionary pathway that enables a pathogen to enhance virulence. Furthermore, the demonstration that cadaverine can inhibit enterotoxin activity may lead to more general models about toxin activity or entry into cells and suggests an avenue for antitoxin therapy. Thus, understanding the role of black holes in pathogen evolution may yield clues to new treatments of infectious diseases.

SUBMITTER: Maurelli AT

PROVIDER: S-EPMC19942 | biostudies-other | 1998 Mar

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.

Maurelli A T AT Fernández R E RE Bloch C A CA Rode C K CK Fasano A A

Proceedings of the National Academy of Sciences of the United States of America 19980301 7

Plasmids, bacteriophages, and pathogenicity islands are genomic additions that contribute to the evolution of bacterial pathogens. For example, Shigella spp., the causative agents of bacillary dysentery, differ from the closely related commensal Escherichia coli in the presence of a plasmid in Shigella that encodes virulence functions. However, pathogenic bacteria also may lack properties that are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is present in approximately 90% ...[more]

PMID: 9520472

Similar Datasets

Project description:BACKGROUND: The Escherichia coli species contains a variety of commensal and pathogenic strains, and its intraspecific diversity is extraordinarily high. With the availability of an increasing number of E. coli strain genomes, a more comprehensive concept of their evolutionary history and ecological adaptation can be developed using phylogenomic analyses. In this study, we constructed two types of whole-genome phylogenies based on 34 E. coli strains using collinear genomic segments. The first phylogeny was based on the concatenated collinear regions shared by all of the studied genomes, and the second phylogeny was based on the variable collinear regions that are absent from at least one genome. Intuitively, the first phylogeny is likely to reveal the lineal evolutionary history among these strains (i.e., an evolutionary phylogeny), whereas the latter phylogeny is likely to reflect the whole-genome similarities of extant strains (i.e., a similarity phylogeny). RESULTS: Within the evolutionary phylogeny, the strains were clustered in accordance with known phylogenetic groups and phenotypes. When comparing evolutionary and similarity phylogenies, a concept emerges that Shigella may have originated from at least three distinct ancestors and evolved into a single clade. By scrutinizing the properties that are shared amongst Shigella strains but missing in other E. coli genomes, we found that the common regions of the Shigella genomes were mainly influenced by mobile genetic elements, implying that they may have experienced convergent evolution via horizontal gene transfer. Based on an inspection of certain key branches of interest, we identified several collinear regions that may be associated with the pathogenicity of specific strains. Moreover, by examining the annotated genes within these regions, further detailed evidence associated with pathogenicity was revealed. CONCLUSIONS: Collinear regions are reliable genomic features used for phylogenomic analysis among closely related genomes while linking the genomic diversity with phenotypic differences in a meaningful way. The pathogenicity of a strain may be associated with both the arrival of virulence factors and the modification of genomes via mutations. Such phylogenomic studies that compare collinear regions of whole genomes will help to better understand the evolution and adaptation of closely related microbes and E. coli in particular.

Project description:BACKGROUND:Diphtheria toxin (DT) is produced by toxigenic strains of the human pathogen Corynebacterium diphtheriae as well as zoonotic C. ulcerans and C. pseudotuberculosis. Toxigenic strains may cause severe respiratory diphtheria, myocarditis, neurological damage or cutaneous diphtheria. The DT encoding tox gene is located in a mobile genomic region and tox variability between C. diphtheriae and C. ulcerans has been postulated based on sequences of a few isolates. In contrast, species-specific sequence analysis of the diphtheria toxin repressor gene (dtxR), occurring both in toxigenic and non-toxigenic Corynebacterium species, has not been done yet. We used whole genome sequencing data from 91 toxigenic and 46 non-toxigenic isolates of different pathogenic Corynebacterium species of animal or human origin to elucidate differences in extracted DT, DtxR and tox-surrounding genetic elements by a phylogenetic analysis in a large sample set. RESULTS:Sequences of both DT and DtxR, extracted from whole genome sequencing data, could be classified in four distinct, nearly species-specific clades, corresponding to C. diphtheriae, C. pseudotuberculosis, C. ulcerans and atypical C. ulcerans from a non-toxigenic toxin gene-bearing wildlife cluster. Average amino acid similarities were above 99% for DT and DtxR within the four groups, but lower between them. For DT, subgroups below species level could be identified, correlating with different tox-comprising mobile genetic elements. In most C. diphtheriae, tox genes were located within known prophages. In contrast, in C. ulcerans diverse tox-including mobile elements could be identified: either prophages differing from C. diphtheriae prophages or an alternative pathogenicity island (PAI) described previously. One isolate showed a different, shorter tox-comprising putative PAI. Beyond the tox-overlapping elements, most isolates harbored a variety of additional prophages. CONCLUSION:Our NGS data from 137 isolates indicate the existence of different genetic backgrounds of DT-mediated pathogenicity in different Corynebacterium species and evolution of once acquired pathogenicity features with the strains. Different groups of pathogenicity-related elements within C. ulcerans imply that tox transmission pathways between isolates may differ in the zoonotic species and contribute to their emerging pathogenic potential.

Dataset Information

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.

Publications

"Black holes" and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure