Pathogenomics of the virulence plasmids of Escherichia coli

Abstract

Bacterial plasmids are self-replicating, extrachromosomal elements that are key agents of change in microbial populations. They promote the dissemination of a variety of traits, including virulence, enhanced fitness, resistance to antimicrobial agents, and metabolism of rare substances. Escherichia coli, perhaps the most studied of microorganisms, has been found to possess a variety of plasmid types. Included among these are plasmids associated with virulence. Several types of E. coli virulence plasmids exist, including those essential for the virulence of enterotoxigenic E. coli, enteroinvasive E. coli, enteropathogenic E. coli, enterohemorrhagic E. coli, enteroaggregative E. coli, and extraintestinal pathogenic E. coli. Despite their diversity, these plasmids belong to a few plasmid backbones that present themselves in a conserved and syntenic manner. Thanks to some recent research, including sequence analysis of several representative plasmid genomes and molecular pathogenesis studies, the evolution of these virulence plasmids and the implications of their acquisition by E. coli are now better understood and appreciated. Here, work involving each of the E. coli virulence plasmid types is summarized, with the available plasmid genomic sequences for several E. coli pathotypes being compared in an effort to understand the evolution of these plasmid types and define their core and accessory components.

FIG. 1.

Linear comparison of RepFIIA and RepI1 virulence plasmids of E. coli. The top two maps are basic RepFIIA and RepI1 backbones, highlighted in orange (RepFIIA) and green (RepI1). These regions are highlighted throughout the figure to illustrate genetic load regions. The scale is in base pairs. Maps begin with either RepFIIA or RepI1 and are drawn to scale. ISs are marked below each map, and virulence genes of interest are marked and colored. The boxed region indicates ETEC plasmids that encode either CS1 or CFA/I. All maps were drawn with XPlasMap (http://www.iayork.com/XPlasMap/index.shtml).

FIG. 2.

Linear comparison of RepFIB/FIIA virulence plasmids of E. coli. The top map is the basic RepFIB/FIIA backbone, with genetic load regions highlighted in orange or blue. These regions are highlighted throughout the figure to illustrate genetic load regions. The scale is in base pairs. Maps begin with either RepFIIA or RepFIC and are drawn to scale. ISs are marked below each map, and virulence genes of interest are marked and colored. Boxed regions indicate EAEC plasmids (top), EPEC plasmids (middle), and EHEC plasmids (bottom).

FIG. 3.

Evolutionary relationships of sequenced aggR (EAEC) and rns (ETEC) genes. The evolutionary history was inferred using the neighbor-joining method (157). Bootstrap consensus trees were inferred from 500 replicates, and branches corresponding to partitions reproduced in fewer than 50% of bootstrap replicates were collapsed. Bootstrap confidence values greater than 50% are listed to the left of the nodes. The tree is drawn to scale proportional to evolutionary distances. Distances were computed using the maximum composite likelihood method (179) and are in units of numbers of base substitutions per site. Phylogenetic analyses were conducted by use of MEGA4 (178).

FIG. 4.

Linear comparison of Inv virulence plasmids of EIEC/Shigella strains. The top map is the basic RepFIB/FIIA backbone, with genetic load regions highlighted in orange or blue. These regions are highlighted throughout the figure to illustrate genetic load regions. The scale is in base pairs. Maps begin with RepFIIA and are drawn to scale. ISs are marked below each map, and virulence genes of interest are marked and colored. Colored lines follow genes of interest throughout the diagram to illustrate gene presence and overall synteny.

FIG. 5.

Evolutionary relationships of concatenated ospD2 and traI genes from Inv plasmids. The evolutionary history was inferred using the neighbor-joining method (157). Bootstrap consensus trees were inferred from 500 replicates, and branches corresponding to partitions reproduced in fewer than 50% of bootstrap replicates were collapsed. Bootstrap confidence values greater than 50% are listed to the left of the nodes. The tree is drawn to scale proportional to evolutionary distances. Distances were computed using the maximum composite likelihood method (179) and are in units of numbers of base substitutions per site. Phylogenetic analyses were conducted by use of MEGA4 (178).

FIG. 6.

Linear comparison of ColV and ColBM virulence plasmids of ExPEC. The top map is the basic RepFIB/FIIA backbone, with genetic load regions highlighted in orange or blue. These regions are highlighted throughout the figure to illustrate genetic load regions. The scale is in base pairs. Maps begin with RepFIIA and are drawn to scale. ISs are marked below each map, and virulence genes of interest are marked and colored. Colored lines follow genes of interest throughout the diagram to illustrate gene presence and overall synteny. NMEC, neonatal meningitis E. coli.

FIG. 7.

Evolutionary relationships of the RepFIB repA gene from RepFIB/FIIA plasmids. The evolutionary history was inferred using the neighbor-joining method (157). Bootstrap consensus trees were inferred from 500 replicates, and branches corresponding to partitions reproduced in fewer than 50% of bootstrap replicates were collapsed. Bootstrap confidence values greater than 50% are listed to the left of the nodes. The tree is drawn to scale proportional to evolutionary distances. Distances were computed using the maximum composite likelihood method (179) and are in units of numbers of base substitutions per site. Phylogenetic analyses were conducted by use of MEGA4 (178). Colored boxes represent the host pathotype source of the plasmid sequenced.

FIG. 8.

Evolutionary relationships of the RepFIIA repA1 gene from RepFIB/FIIA and RepFIIA plasmids. The evolutionary history was inferred by using the neighbor-joining method (157). Bootstrap consensus trees were inferred from 500 replicates, and branches corresponding to partitions reproduced in fewer than 50% of bootstrap replicates were collapsed. Bootstrap confidence values greater than 50% are listed to the left of the nodes. The tree is drawn to scale proportional to evolutionary distances. Distances were computed by using the maximum composite likelihood method (179) and are in units of numbers of base substitutions per site. Phylogenetic analyses were conducted by use of MEGA4 (178). Colored boxes represent the host pathotype source of the plasmid sequenced.

FIG. 9.

Evolutionary relationships of the RepIa repZ gene from sequenced RepI1 plasmids. The evolutionary history was inferred by using the neighbor-joining method (157). Bootstrap consensus trees were inferred from 500 replicates, and branches corresponding to partitions reproduced in fewer than 50% of bootstrap replicates were collapsed. Bootstrap confidence values greater than 50% are listed to the left of the nodes. The tree is drawn to scale proportional to evolutionary distances. Distances were computed by using the maximum composite likelihood method (179) and are in units of numbers of base substitutions per site. Phylogenetic analyses were conducted by use of MEGA4 (178).