Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections

Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI). Surface adhesins play an important role in the primary attachment to plasma proteins that coat the surface of prosthetic devices after implantation. Previous efforts to identify a genetic component of the bacterium that c...

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Autores: Morales Laverde, Liliana Andrea, Trobos, Margarita, Echeverz Sarasúa, Maite, Solano Goñi, Cristina, Lasa Uzcudun, Íñigo
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:Universidad San Jorge (USJ)
Repositório:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/44821
Acesso em linha:https://hdl.handle.net/2454/44821
Access Level:Acceso aberto
Palavra-chave:Periprosthetic joint infection
LPXTG proteins
SNPs
Intergenic regions
Staphylococcus aureus
Biofilm
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spelling Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infectionsMorales Laverde, Liliana AndreaTrobos, MargaritaEcheverz Sarasúa, MaiteSolano Goñi, CristinaLasa Uzcudun, ÍñigoPeriprosthetic joint infectionLPXTG proteinsSNPsIntergenic regionsStaphylococcus aureusBiofilmStaphylococcus aureus is a leading cause of prosthetic joint infections (PJI). Surface adhesins play an important role in the primary attachment to plasma proteins that coat the surface of prosthetic devices after implantation. Previous efforts to identify a genetic component of the bacterium that confers an enhanced capacity to cause PJI have focused on gene content, kmers, or single-nucleotide polymorphisms (SNPs) in coding sequences. Here, using a collection of S. aureus strains isolated from PJI and wounds, we investigated whether genetic variations in the regulatory region of genes encoding surface adhesins lead to differences in their expression levels and modulate the capacity of S. aureus to colonize implanted prosthetic devices. The data revealed that S. aureus isolates from the same clonal complex (CC) contain a specific pattern of SNPs in the regulatory region of genes encoding surface adhesins. As a consequence, each clonal lineage shows a specific profile of surface proteins expression. Co-infection experiments with representative isolates of the most prevalent CCs demonstrated that some lineages have a higher capacity to colonize implanted catheters in a murine infection model, which correlated with a greater ability to form a biofilm on coated surfaces with plasma proteins. Together, results indicate that differences in the expression level of surface adhesins may modulate the propensity of S. aureus strains to cause PJI. Given the high conservation of surface proteins among staphylococci, our work lays the framework for investigating how diversification at intergenic regulatory regions affects the capacity of S. aureus to colonize the surface of medical implants.This work was financially supported by the Spanish Ministry of Science and Innovation grant PID2020-113494RB-I00 to I.L. (Agencia Española de Investigación/Fondo Europeo de Desarrollo Regional, European Union), the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 754412 [MoRE2020 - Region Väs-tra Götaland], and the IngaBritt and Arne Lundberg Foundation (LU2021-0048). L.M.L was supported by the European Union's H2020 research and innovation programme under Marie Sklodowska-Curie grant agreement No 801586 (IberusTalent).ElsevierCiencias de la SaludOsasun Zientziak2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/mswordhttps://hdl.handle.net/2454/44821reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarrainstname:Universidad San Jorge (USJ)Inglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113494RB-I00info:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/754412info:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/801586© 2022 The Authors. This is an open access article under the CC BY-NC-ND license.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:academica-e.unavarra.es:2454/448212026-06-17T12:41:47Z
dc.title.none.fl_str_mv Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
title Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
spellingShingle Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
Morales Laverde, Liliana Andrea
Periprosthetic joint infection
LPXTG proteins
SNPs
Intergenic regions
Staphylococcus aureus
Biofilm
title_short Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
title_full Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
title_fullStr Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
title_full_unstemmed Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
title_sort Functional analysis of intergenic regulatory regions of genes encoding surface adhesins in Staphylococcus aureus isolates from periprosthetic joint infections
dc.creator.none.fl_str_mv Morales Laverde, Liliana Andrea
Trobos, Margarita
Echeverz Sarasúa, Maite
Solano Goñi, Cristina
Lasa Uzcudun, Íñigo
author Morales Laverde, Liliana Andrea
author_facet Morales Laverde, Liliana Andrea
Trobos, Margarita
Echeverz Sarasúa, Maite
Solano Goñi, Cristina
Lasa Uzcudun, Íñigo
author_role author
author2 Trobos, Margarita
Echeverz Sarasúa, Maite
Solano Goñi, Cristina
Lasa Uzcudun, Íñigo
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ciencias de la Salud
Osasun Zientziak
dc.subject.none.fl_str_mv Periprosthetic joint infection
LPXTG proteins
SNPs
Intergenic regions
Staphylococcus aureus
Biofilm
topic Periprosthetic joint infection
LPXTG proteins
SNPs
Intergenic regions
Staphylococcus aureus
Biofilm
description Staphylococcus aureus is a leading cause of prosthetic joint infections (PJI). Surface adhesins play an important role in the primary attachment to plasma proteins that coat the surface of prosthetic devices after implantation. Previous efforts to identify a genetic component of the bacterium that confers an enhanced capacity to cause PJI have focused on gene content, kmers, or single-nucleotide polymorphisms (SNPs) in coding sequences. Here, using a collection of S. aureus strains isolated from PJI and wounds, we investigated whether genetic variations in the regulatory region of genes encoding surface adhesins lead to differences in their expression levels and modulate the capacity of S. aureus to colonize implanted prosthetic devices. The data revealed that S. aureus isolates from the same clonal complex (CC) contain a specific pattern of SNPs in the regulatory region of genes encoding surface adhesins. As a consequence, each clonal lineage shows a specific profile of surface proteins expression. Co-infection experiments with representative isolates of the most prevalent CCs demonstrated that some lineages have a higher capacity to colonize implanted catheters in a murine infection model, which correlated with a greater ability to form a biofilm on coated surfaces with plasma proteins. Together, results indicate that differences in the expression level of surface adhesins may modulate the propensity of S. aureus strains to cause PJI. Given the high conservation of surface proteins among staphylococci, our work lays the framework for investigating how diversification at intergenic regulatory regions affects the capacity of S. aureus to colonize the surface of medical implants.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2454/44821
url https://hdl.handle.net/2454/44821
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113494RB-I00
info:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/754412
info:eu-repo/grantAgreement/European Commission/Horizon 2020 Framework Programme/801586
dc.rights.none.fl_str_mv © 2022 The Authors. This is an open access article under the CC BY-NC-ND license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © 2022 The Authors. This is an open access article under the CC BY-NC-ND license.
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/msword
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
instname:Universidad San Jorge (USJ)
instname_str Universidad San Jorge (USJ)
reponame_str Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
collection Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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