Exfoliative toxin E, a new Staphylococcus aureus virulence factor with host-specific activity

Detalhes bibliográficos
Autor(a) principal: Imanishi, Ichiro
Data de Publicação: 2019
Outros Autores: 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
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.
id UNSP_1d51cd917e7a305a7b642aa13cdbd2f2
oai_identifier_str oai:repositorio.unesp.br:11449/198109
network_acronym_str UNSP
network_name_str Repositório Institucional da UNESP
repository_id_str 2946
spelling 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
_version_ 1808129341670817792