The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates

Ruth M Kennan, Wilson Wong, Om Dhungyel, Xiao Han, David M Wong, Dane Parker, Carlos J Rosado, Ruby HP Law, Sheena McGowan, Shane B Reeve, Vitalina Levina, Glenn A Powers, Robert N Pike, Stephen P Bottomley, Alexander Ian Smith, Ian Marsh, Richard J Whittington, James Whisstock, Corrine J Porter, Julian I Rood

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus is the causative agent of ovine footrot, a highly contagious disease that is characterized by the separation of the hoof from the underlying tissue. D. nodosus secretes three subtilisin-like proteases whose analysis forms the basis of diagnostic tests that differentiate between virulent and benign strains and have been postulated to play a role in virulence. We have constructed protease mutants of D. nodosus; their analysis in a sheep virulence model revealed that one of these enzymes, AprV2, was required for virulence. These studies challenge the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with aprB2, which encodes a variant that has impaired elastase activity. We have determined the crystal structures of both AprV2 and AprB2 and characterized the biological activity of these enzymes. These data reveal..
Original languageEnglish
Pages (from-to)1 - 12
Number of pages12
JournalPLoS Pathogens
Volume6
Issue number11
DOIs
Publication statusPublished - 2010

Cite this

Kennan, Ruth M ; Wong, Wilson ; Dhungyel, Om ; Han, Xiao ; Wong, David M ; Parker, Dane ; Rosado, Carlos J ; Law, Ruby HP ; McGowan, Sheena ; Reeve, Shane B ; Levina, Vitalina ; Powers, Glenn A ; Pike, Robert N ; Bottomley, Stephen P ; Smith, Alexander Ian ; Marsh, Ian ; Whittington, Richard J ; Whisstock, James ; Porter, Corrine J ; Rood, Julian I. / The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates. In: PLoS Pathogens. 2010 ; Vol. 6, No. 11. pp. 1 - 12.
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title = "The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates",
abstract = "Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus is the causative agent of ovine footrot, a highly contagious disease that is characterized by the separation of the hoof from the underlying tissue. D. nodosus secretes three subtilisin-like proteases whose analysis forms the basis of diagnostic tests that differentiate between virulent and benign strains and have been postulated to play a role in virulence. We have constructed protease mutants of D. nodosus; their analysis in a sheep virulence model revealed that one of these enzymes, AprV2, was required for virulence. These studies challenge the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with aprB2, which encodes a variant that has impaired elastase activity. We have determined the crystal structures of both AprV2 and AprB2 and characterized the biological activity of these enzymes. These data reveal..",
author = "Kennan, {Ruth M} and Wilson Wong and Om Dhungyel and Xiao Han and Wong, {David M} and Dane Parker and Rosado, {Carlos J} and Law, {Ruby HP} and Sheena McGowan and Reeve, {Shane B} and Vitalina Levina and Powers, {Glenn A} and Pike, {Robert N} and Bottomley, {Stephen P} and Smith, {Alexander Ian} and Ian Marsh and Whittington, {Richard J} and James Whisstock and Porter, {Corrine J} and Rood, {Julian I}",
year = "2010",
doi = "10.1371/journal.ppat.1001210",
language = "English",
volume = "6",
pages = "1 -- 12",
journal = "PLoS Pathogens",
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Kennan, RM, Wong, W, Dhungyel, O, Han, X, Wong, DM, Parker, D, Rosado, CJ, Law, RHP, McGowan, S, Reeve, SB, Levina, V, Powers, GA, Pike, RN, Bottomley, SP, Smith, AI, Marsh, I, Whittington, RJ, Whisstock, J, Porter, CJ & Rood, JI 2010, 'The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates', PLoS Pathogens, vol. 6, no. 11, pp. 1 - 12. https://doi.org/10.1371/journal.ppat.1001210

The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates. / Kennan, Ruth M; Wong, Wilson; Dhungyel, Om; Han, Xiao; Wong, David M; Parker, Dane; Rosado, Carlos J; Law, Ruby HP; McGowan, Sheena; Reeve, Shane B; Levina, Vitalina; Powers, Glenn A; Pike, Robert N; Bottomley, Stephen P; Smith, Alexander Ian; Marsh, Ian; Whittington, Richard J; Whisstock, James; Porter, Corrine J; Rood, Julian I.

In: PLoS Pathogens, Vol. 6, No. 11, 2010, p. 1 - 12.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates

AU - Kennan, Ruth M

AU - Wong, Wilson

AU - Dhungyel, Om

AU - Han, Xiao

AU - Wong, David M

AU - Parker, Dane

AU - Rosado, Carlos J

AU - Law, Ruby HP

AU - McGowan, Sheena

AU - Reeve, Shane B

AU - Levina, Vitalina

AU - Powers, Glenn A

AU - Pike, Robert N

AU - Bottomley, Stephen P

AU - Smith, Alexander Ian

AU - Marsh, Ian

AU - Whittington, Richard J

AU - Whisstock, James

AU - Porter, Corrine J

AU - Rood, Julian I

PY - 2010

Y1 - 2010

N2 - Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus is the causative agent of ovine footrot, a highly contagious disease that is characterized by the separation of the hoof from the underlying tissue. D. nodosus secretes three subtilisin-like proteases whose analysis forms the basis of diagnostic tests that differentiate between virulent and benign strains and have been postulated to play a role in virulence. We have constructed protease mutants of D. nodosus; their analysis in a sheep virulence model revealed that one of these enzymes, AprV2, was required for virulence. These studies challenge the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with aprB2, which encodes a variant that has impaired elastase activity. We have determined the crystal structures of both AprV2 and AprB2 and characterized the biological activity of these enzymes. These data reveal..

AB - Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus is the causative agent of ovine footrot, a highly contagious disease that is characterized by the separation of the hoof from the underlying tissue. D. nodosus secretes three subtilisin-like proteases whose analysis forms the basis of diagnostic tests that differentiate between virulent and benign strains and have been postulated to play a role in virulence. We have constructed protease mutants of D. nodosus; their analysis in a sheep virulence model revealed that one of these enzymes, AprV2, was required for virulence. These studies challenge the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with aprB2, which encodes a variant that has impaired elastase activity. We have determined the crystal structures of both AprV2 and AprB2 and characterized the biological activity of these enzymes. These data reveal..

UR - http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001210

U2 - 10.1371/journal.ppat.1001210

DO - 10.1371/journal.ppat.1001210

M3 - Article

VL - 6

SP - 1

EP - 12

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 11

ER -