Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patie...

Autores
Di Gregorio, Sabrina Noelia; Weltman, Gabriela; Fabbri, Carolina; Fernández, Silvina; Zárate, Soledad; Smayevsky, Jorgelina; Power, Pablo; Campos, Josefina; Llarrull, Leticia Irene; Mollerach, Marta Eugenia
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive ep-isodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mecA/mecC genes, and had reduced susceptibility to teicoplanin. SA2 showed higher b-lactamase activity than SAMS1. However, b-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbi-ologists in the region, as MIONSA detection and treatment represent an important clinical challenge.
Fil: Di Gregorio, Sabrina Noelia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Weltman, Gabriela. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;
Fil: Fabbri, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Fernández, Silvina. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;
Fil: Zárate, Soledad. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina
Fil: Smayevsky, Jorgelina. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina
Fil: Power, Pablo. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Campos, Josefina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Mollerach, Marta Eugenia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Staphylococcus aureus
MIONSA
WGS
ST8
PBP2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/265764
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/265764
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with BacteremiaDi Gregorio, Sabrina NoeliaWeltman, GabrielaFabbri, CarolinaFernández, SilvinaZárate, SoledadSmayevsky, JorgelinaPower, PabloCampos, JosefinaLlarrull, Leticia IreneMollerach, Marta EugeniaStaphylococcus aureusMIONSAWGSST8PBP2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive ep-isodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mecA/mecC genes, and had reduced susceptibility to teicoplanin. SA2 showed higher b-lactamase activity than SAMS1. However, b-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbi-ologists in the region, as MIONSA detection and treatment represent an important clinical challenge.Fil: Di Gregorio, Sabrina Noelia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Weltman, Gabriela. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;Fil: Fabbri, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Fernández, Silvina. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;Fil: Zárate, Soledad. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Smayevsky, Jorgelina. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Power, Pablo. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Campos, Josefina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mollerach, Marta Eugenia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaMDPI2024-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265764Di Gregorio, Sabrina Noelia; Weltman, Gabriela; Fabbri, Carolina; Fernández, Silvina; Zárate, Soledad ; et al.; Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia; MDPI; Antibiotics; 13; 6; 6-2024; 554-5712079-6382CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/antibiotics13060554info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:21:50Zoai:ri.conicet.gov.ar:11336/265764instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:21:50.719CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
title Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
spellingShingle Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
Di Gregorio, Sabrina Noelia
Staphylococcus aureus
MIONSA
WGS
ST8
PBP2
title_short Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
title_full Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
title_fullStr Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
title_full_unstemmed Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
title_sort Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
dc.creator.none.fl_str_mv Di Gregorio, Sabrina Noelia
Weltman, Gabriela
Fabbri, Carolina
Fernández, Silvina
Zárate, Soledad
Smayevsky, Jorgelina
Power, Pablo
Campos, Josefina
Llarrull, Leticia Irene
Mollerach, Marta Eugenia
author Di Gregorio, Sabrina Noelia
author_facet Di Gregorio, Sabrina Noelia
Weltman, Gabriela
Fabbri, Carolina
Fernández, Silvina
Zárate, Soledad
Smayevsky, Jorgelina
Power, Pablo
Campos, Josefina
Llarrull, Leticia Irene
Mollerach, Marta Eugenia
author_role author
author2 Weltman, Gabriela
Fabbri, Carolina
Fernández, Silvina
Zárate, Soledad
Smayevsky, Jorgelina
Power, Pablo
Campos, Josefina
Llarrull, Leticia Irene
Mollerach, Marta Eugenia
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Staphylococcus aureus
MIONSA
WGS
ST8
PBP2
topic Staphylococcus aureus
MIONSA
WGS
ST8
PBP2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive ep-isodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mecA/mecC genes, and had reduced susceptibility to teicoplanin. SA2 showed higher b-lactamase activity than SAMS1. However, b-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbi-ologists in the region, as MIONSA detection and treatment represent an important clinical challenge.
Fil: Di Gregorio, Sabrina Noelia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Weltman, Gabriela. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;
Fil: Fabbri, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Fernández, Silvina. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires;
Fil: Zárate, Soledad. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina
Fil: Smayevsky, Jorgelina. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina
Fil: Power, Pablo. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Campos, Josefina. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Mollerach, Marta Eugenia. Instituto de Investigaciones En Bacteriologia y Virologia Molecular (ibavim) ; Facultad de Farmacia y Bioquimica ; Universidad de Buenos Aires; . Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive ep-isodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mecA/mecC genes, and had reduced susceptibility to teicoplanin. SA2 showed higher b-lactamase activity than SAMS1. However, b-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbi-ologists in the region, as MIONSA detection and treatment represent an important clinical challenge.
publishDate 2024
dc.date.none.fl_str_mv 2024-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/265764
Di Gregorio, Sabrina Noelia; Weltman, Gabriela; Fabbri, Carolina; Fernández, Silvina; Zárate, Soledad ; et al.; Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia; MDPI; Antibiotics; 13; 6; 6-2024; 554-571
2079-6382
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265764
identifier_str_mv Di Gregorio, Sabrina Noelia; Weltman, Gabriela; Fabbri, Carolina; Fernández, Silvina; Zárate, Soledad ; et al.; Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia; MDPI; Antibiotics; 13; 6; 6-2024; 554-571
2079-6382
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/antibiotics13060554
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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