Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1038/s41598-019-52777-3 http://hdl.handle.net/11449/198109 |
Resumo: | Exfoliative toxins (ETs) are secreted virulence factors produced by staphylococci. These serine proteases specifically cleave desmoglein 1 (Dsg1) in mammals and are key elements in staphylococcal skin infections. We recently identified a new et gene in S. aureus O46, a strain isolated from ovine mastitis. In the present study, we characterized the new et gene at a genetic level and the enzymatic activity of the deduced protein. The S. aureus O46 genome was re-assembled, annotated and compared with other publicly available S. aureus genomes. The deduced amino acid sequence of the new et gene shared 40%, 53% and 59% sequence identity to those of ETA, ETB and ETD, respectively. The new et gene shared the same genetic vicinity and was similar in other S. aureus strains bearing this gene. The recombinant enzyme of the new et gene caused skin exfoliation in vivo in neonatal mice. The new et-gene was thus named ete, encoding a new type (type E) of exfoliative toxin. We showed that ETE degraded the extracellular segments of Dsg1 in murine, ovine and caprine epidermis, as well as in ovine teat canal epithelia, but not that in bovine epidermis. We further showed that it directly hydrolyzed human and swine Dsg1 as well as murine Dsg1α and Dsg1β, but not canine Dsg1 or murine Dsg1γ. Molecular modeling revealed a correlation between the preferred orientation of ETE docking on its Dsg1 cleavage site and species-specific cleavage activity, suggesting that the docking step preceding cleavage accounts for the ETE species-specificity. This new virulence factor may contribute to the bacterial colonization on the stratified epithelia in certain ruminants with mastitis. |
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Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activityExfoliative toxins (ETs) are secreted virulence factors produced by staphylococci. These serine proteases specifically cleave desmoglein 1 (Dsg1) in mammals and are key elements in staphylococcal skin infections. We recently identified a new et gene in S. aureus O46, a strain isolated from ovine mastitis. In the present study, we characterized the new et gene at a genetic level and the enzymatic activity of the deduced protein. The S. aureus O46 genome was re-assembled, annotated and compared with other publicly available S. aureus genomes. The deduced amino acid sequence of the new et gene shared 40%, 53% and 59% sequence identity to those of ETA, ETB and ETD, respectively. The new et gene shared the same genetic vicinity and was similar in other S. aureus strains bearing this gene. The recombinant enzyme of the new et gene caused skin exfoliation in vivo in neonatal mice. The new et-gene was thus named ete, encoding a new type (type E) of exfoliative toxin. We showed that ETE degraded the extracellular segments of Dsg1 in murine, ovine and caprine epidermis, as well as in ovine teat canal epithelia, but not that in bovine epidermis. We further showed that it directly hydrolyzed human and swine Dsg1 as well as murine Dsg1α and Dsg1β, but not canine Dsg1 or murine Dsg1γ. Molecular modeling revealed a correlation between the preferred orientation of ETE docking on its Dsg1 cleavage site and species-specific cleavage activity, suggesting that the docking step preceding cleavage accounts for the ETE species-specificity. This new virulence factor may contribute to the bacterial colonization on the stratified epithelia in certain ruminants with mastitis.Laboratory of Veterinary Internal Medicine Division of Animal Life Science Graduate School Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-choSTLO INRA Agrocampus OuestCellular and Molecular Genetics Laboratory Institute of Biological Sciences Federal University of Minas Gerais Belo HorizonteIBILCE/UNESPInstitute of Health Sciences Federal University of BahiaInstitute of Biology Federal University of BahiaIBILCE/UNESPTokyo University of Agriculture and TechnologyAgrocampus OuestUniversidade Federal de Minas Gerais (UFMG)Universidade Estadual Paulista (Unesp)Universidade Federal da Bahia (UFBA)Imanishi, IchiroNicolas, AurélieCaetano, Ana-Carolina BarbosaCastro, Thiago Luiz de PaulaTartaglia, Natayme RochaMariutti, Ricardo [UNESP]Guédon, EricEven, SergineBerkova, NadiaArni, Raghuvir K. [UNESP]Seyffert, NubiaAzevedo, VascoNishifuji, KojiLe Loir, Yves2020-12-12T00:59:27Z2020-12-12T00:59:27Z2019-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-52777-3Scientific Reports, v. 9, n. 1, 2019.2045-2322http://hdl.handle.net/11449/19810910.1038/s41598-019-52777-32-s2.0-8507472613791625089789458870000-0003-2460-1145Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reportsinfo:eu-repo/semantics/openAccess2021-10-23T08:46:56Zoai:repositorio.unesp.br:11449/198109Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:37:05.816494Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
title |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
spellingShingle |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity Imanishi, Ichiro |
title_short |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
title_full |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
title_fullStr |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
title_full_unstemmed |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
title_sort |
Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity |
author |
Imanishi, Ichiro |
author_facet |
Imanishi, Ichiro Nicolas, Aurélie Caetano, Ana-Carolina Barbosa Castro, Thiago Luiz de Paula Tartaglia, Natayme Rocha Mariutti, Ricardo [UNESP] Guédon, Eric Even, Sergine Berkova, Nadia Arni, Raghuvir K. [UNESP] Seyffert, Nubia Azevedo, Vasco Nishifuji, Koji Le Loir, Yves |
author_role |
author |
author2 |
Nicolas, Aurélie Caetano, Ana-Carolina Barbosa Castro, Thiago Luiz de Paula Tartaglia, Natayme Rocha Mariutti, Ricardo [UNESP] Guédon, Eric Even, Sergine Berkova, Nadia Arni, Raghuvir K. [UNESP] Seyffert, Nubia Azevedo, Vasco Nishifuji, Koji Le Loir, Yves |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Tokyo University of Agriculture and Technology Agrocampus Ouest Universidade Federal de Minas Gerais (UFMG) Universidade Estadual Paulista (Unesp) Universidade Federal da Bahia (UFBA) |
dc.contributor.author.fl_str_mv |
Imanishi, Ichiro Nicolas, Aurélie Caetano, Ana-Carolina Barbosa Castro, Thiago Luiz de Paula Tartaglia, Natayme Rocha Mariutti, Ricardo [UNESP] Guédon, Eric Even, Sergine Berkova, Nadia Arni, Raghuvir K. [UNESP] Seyffert, Nubia Azevedo, Vasco Nishifuji, Koji Le Loir, Yves |
description |
Exfoliative toxins (ETs) are secreted virulence factors produced by staphylococci. These serine proteases specifically cleave desmoglein 1 (Dsg1) in mammals and are key elements in staphylococcal skin infections. We recently identified a new et gene in S. aureus O46, a strain isolated from ovine mastitis. In the present study, we characterized the new et gene at a genetic level and the enzymatic activity of the deduced protein. The S. aureus O46 genome was re-assembled, annotated and compared with other publicly available S. aureus genomes. The deduced amino acid sequence of the new et gene shared 40%, 53% and 59% sequence identity to those of ETA, ETB and ETD, respectively. The new et gene shared the same genetic vicinity and was similar in other S. aureus strains bearing this gene. The recombinant enzyme of the new et gene caused skin exfoliation in vivo in neonatal mice. The new et-gene was thus named ete, encoding a new type (type E) of exfoliative toxin. We showed that ETE degraded the extracellular segments of Dsg1 in murine, ovine and caprine epidermis, as well as in ovine teat canal epithelia, but not that in bovine epidermis. We further showed that it directly hydrolyzed human and swine Dsg1 as well as murine Dsg1α and Dsg1β, but not canine Dsg1 or murine Dsg1γ. Molecular modeling revealed a correlation between the preferred orientation of ETE docking on its Dsg1 cleavage site and species-specific cleavage activity, suggesting that the docking step preceding cleavage accounts for the ETE species-specificity. This new virulence factor may contribute to the bacterial colonization on the stratified epithelia in certain ruminants with mastitis. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-01 2020-12-12T00:59:27Z 2020-12-12T00:59:27Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1038/s41598-019-52777-3 Scientific Reports, v. 9, n. 1, 2019. 2045-2322 http://hdl.handle.net/11449/198109 10.1038/s41598-019-52777-3 2-s2.0-85074726137 9162508978945887 0000-0003-2460-1145 |
url |
http://dx.doi.org/10.1038/s41598-019-52777-3 http://hdl.handle.net/11449/198109 |
identifier_str_mv |
Scientific Reports, v. 9, n. 1, 2019. 2045-2322 10.1038/s41598-019-52777-3 2-s2.0-85074726137 9162508978945887 0000-0003-2460-1145 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Scientific Reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1808129341670817792 |