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Category: Clinical Microbiology
Virulence Plasmids of Spore-Forming Bacteria, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555818982/9781555818975_Chap27-1.gif /docserver/preview/fulltext/10.1128/9781555818982/9781555818975_Chap27-2.gifAbstract:
Spore-forming bacteria cause some of the most significant diseases of both humans and animals, including tetanus, botulism, gas gangrene, anthrax, and many different enteric or gastroenteritis syndromes. The pathogenesis of most of these diseases involves the production of potent protein toxins, including tetanus and botulinum toxins, anthrax toxin, and alpha-toxin, epsilon-toxin (ETX), and enterotoxin (CPE) from Clostridium perfringens. The genes for many of these toxins, as well as other virulence factors such as the capsule biosynthesis genes of Bacillus anthracis, are located on plasmids, with examples including the tetanus toxin plasmid, the conjugative toxin plasmids of C. perfringens, and the pXO1 and pXO2 virulence plasmids from B. anthracis ( 1 ). In this chapter we will review our knowledge of these plasmids, the virulence factors that they encode, and their role in disease.
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Comparative alignment of C. perfringens plasmids. Open reading frames (ORFs) are indicated by arrows as follows: red, the tcp locus; dark blue, other shared ORFs; light purple, tetracycline resistance genes; green, the cpb2 toxin gene; purple, the netB toxin gene; pink, the etx gene; gray, the cpe gene; dark gray, the iota-toxin gene; yellow, plasmid replication region; light blue, regions unique to each plasmid. Asterisks denote a toxin gene. Reproduced with permission from reference 4 .
Phylogenetic analysis of ParM variants. The phylogenetic tree was constructed using the amino acid sequences of ParM proteins identified using BlastP searches of the nonredundant NCBI protein database. The phylogenetic tree was constructed using the phylogeny analysis software: http://www.phylogeny.fr/version2_cgi/index.cgi ( 171 , 172 ). The JGS1495, JGS1987, and ATCC3626 sequences are from genome sequencing projects and yielded multiple ParM homologues from putative plasmid sequences; each ParM homologue was named according to its ParM group.
Plasmid maps of toxin plasmids from spore-forming bacteria. The circular maps of the B. anthracis toxin plasmids, pXO1 (AF065404) and pXO2 (AF188935), the C. tetani neurotoxin plasmid pE88 (AF528077), and the conjugative group I (pCLJ, CP001081) and group II (pCLL, CP001057) C. botulinum neurotoxin plasmids are shown. Predicted ORFs are depicted as black arrows or bars along the circular maps. Regions of interest are indicated inside the plasmid circles, such as the pathogenicity islands present on pXO1 and pXO2. Genes of interest are indicated on the outside of the plasmid maps. Gene names are italicized, while ORFs with similarity to known proteins (such as IS elements) are not italicized. The two neurotoxin loci encoded on the pCLJ plasmid are enlarged showing an example of an orfX neurotoxin locus (bontA region, top) and a ha neurotoxin locus (bontB region, bottom); see text.
Genetic organization of the cpe gene regions. Organization of plasmid-borne (A) and (B) chromosomal cpe loci from C. perfringens. cpe genes are indicated by red arrows, iap and ibp genes by purple arrows, and dcm genes by yellow arrows. Related IS elements are indicated by identical colors. Reproduced with permission from reference 4 .
Comparative alignment of etx loci. The two etx (yellow arrows) loci from plasmid pCP8533etx and strain CN1675 are compared to the location of the cpe (yellow arrow) gene and surrounding sequences in plasmid pCPF5603. The aligned region begins with the dcm gene (left side) found downstream of the tcp locus in all sequenced plasmids. Genes (or DNA sequences) with greater than 90% nucleotide identity are colored alike (except for the cpe and etx genes; both are in yellow but are not related). The genes inside the green boxes appear to have been duplicated and flank the etx locus in plasmid pCP8533etx. Numbers are the CDS designations from the respective sequences: pCPF5603 (accession number: NC_007773), pCP8533etx (accession number: NC_011412), and CN1675 (accession number: EU852100). Arrows without numbers represent pseudogenes.
Genetic conservation of cpb2 locus. Labeled arrows indicate the cpb2 locus from pCP8533etx: resP encoding a putative resolvase, sig encoding a putative signal peptidase I, the cpb2 gene, two hypothetical genes (H1 and H2), and a conserved hypothetical (pCW3_08). Below the locus are heavy lines indicating nucleotide sequence homology of 68% (pCP13) or >95% (all others). The gray lines indicate gaps in the sequence alignment where the sequence is absent from that particular plasmid sequence. Whether the cpb2 gene is present in each plasmid is indicated on the right.
Comparative genetic organization of pXO2, pAW63, and pBT9727. Shared regions are indicated by shaded segments. The pathogenicity island on pXO2 is raised above the map. Reproduced from reference 148 with permission of the authors.