Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci

Edward C Couchman, Hilary P Browne, Matt Dunn, Trevor D Lawley, J Glenn Songer, Val Hall, Liljana Petrovska, Callum Vidor, Milena M Awad, Dena Lyras, Neil F Fairweather

Research output: Contribution to journalArticleResearchpeer-review

Abstract

BACKGROUND: Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised. RESULTS: Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied. CONCLUSIONS: Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.
Original languageEnglish
Article number392
Number of pages13
JournalBMC Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - 16 May 2015

Keywords

  • Clostridium sordellii
  • Large Clostridial Cytotoxin
  • PaLoc
  • Plasmid

Cite this

Couchman, E. C., Browne, H. P., Dunn, M., Lawley, T. D., Songer, J. G., Hall, V., ... Fairweather, N. F. (2015). Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci. BMC Genomics, 16(1), [392]. https://doi.org/10.1186/s12864-015-1613-2
Couchman, Edward C ; Browne, Hilary P ; Dunn, Matt ; Lawley, Trevor D ; Songer, J Glenn ; Hall, Val ; Petrovska, Liljana ; Vidor, Callum ; Awad, Milena M ; Lyras, Dena ; Fairweather, Neil F. / Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci. In: BMC Genomics. 2015 ; Vol. 16, No. 1.
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abstract = "BACKGROUND: Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised. RESULTS: Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied. CONCLUSIONS: Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.",
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author = "Couchman, {Edward C} and Browne, {Hilary P} and Matt Dunn and Lawley, {Trevor D} and Songer, {J Glenn} and Val Hall and Liljana Petrovska and Callum Vidor and Awad, {Milena M} and Dena Lyras and Fairweather, {Neil F}",
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Couchman, EC, Browne, HP, Dunn, M, Lawley, TD, Songer, JG, Hall, V, Petrovska, L, Vidor, C, Awad, MM, Lyras, D & Fairweather, NF 2015, 'Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci' BMC Genomics, vol. 16, no. 1, 392. https://doi.org/10.1186/s12864-015-1613-2

Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci. / Couchman, Edward C; Browne, Hilary P; Dunn, Matt; Lawley, Trevor D; Songer, J Glenn; Hall, Val; Petrovska, Liljana; Vidor, Callum; Awad, Milena M; Lyras, Dena; Fairweather, Neil F.

In: BMC Genomics, Vol. 16, No. 1, 392, 16.05.2015.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci

AU - Couchman, Edward C

AU - Browne, Hilary P

AU - Dunn, Matt

AU - Lawley, Trevor D

AU - Songer, J Glenn

AU - Hall, Val

AU - Petrovska, Liljana

AU - Vidor, Callum

AU - Awad, Milena M

AU - Lyras, Dena

AU - Fairweather, Neil F

PY - 2015/5/16

Y1 - 2015/5/16

N2 - BACKGROUND: Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised. RESULTS: Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied. CONCLUSIONS: Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.

AB - BACKGROUND: Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised. RESULTS: Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied. CONCLUSIONS: Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.

KW - Clostridium sordellii

KW - Large Clostridial Cytotoxin

KW - PaLoc

KW - Plasmid

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U2 - 10.1186/s12864-015-1613-2

DO - 10.1186/s12864-015-1613-2

M3 - Article

VL - 16

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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ER -