Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies

Autores
Acosta, Rocío Belén; Durantini, Edgardo Néstor; Spesia, Mariana Belen
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Photodynamic inactivation (PDI) represents a promising strategy to overcome bacterial resistance by combining light, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) that damage essential cellular components. Combining PDI with conventional antibiotics (ATBs) may further enhance bacterial eradication through complementary mechanisms. In this study, the tetracationic 5,10,15,20-tetra(4-N,N,Ntrimethylammoniophenyl)porphyrin (TMAP4+) was evaluated in combination with ATBs: ampicillin (AMP) and rifampicin (RIF) against Staphylococcus aureus and cephalexin (CFX) against Escherichia coli. The photostability of all agents was assessed under the experimental irradiation conditions, and no evidence of physical interaction between TMAP4+ and the ATBs was detected. AMP and CFX remained photostable, while RIF exhibited only minimal photodegradation under white light, confirming its stability during PDI treatments. The antimicrobial assays revealed that irradiation significantly enhanced the bactericidal activity of TMAP4+. When combined with ATBs, photoactivated TMAP4+ led to a pronounced reduction in the minimum inhibitory concentration (MIC) values of AMP and RIF for S. aureus and of CFX for E. coli, indicating additive effects. Growth curve analyses corroborated these results, showing delayed bacterial growth and decreased maximal optical densities in the combined treatments compared to single agents. Overall, these findings demonstrate that the photodynamic process can potentiate the antimicrobial effect of conventional ATBs without compromising their stability, supporting the potential of PS–ATB combination therapies as a valuable approach to improve antibacterial efficacy and mitigate ATB resistance.
Fil: Acosta, Rocío Belén. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
Fil: Durantini, Edgardo Néstor. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
Fil: Spesia, Mariana Belen. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
Materia
PORPHYRIN
PHOTOSENSITIZER
PHOTOINACTIVATION
ANTIBIOTIC
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:11336/281552

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network_name_str CONICET Digital (CONICET)
spelling Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination TherapiesAcosta, Rocío BelénDurantini, Edgardo NéstorSpesia, Mariana BelenPORPHYRINPHOTOSENSITIZERPHOTOINACTIVATIONANTIBIOTIChttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Photodynamic inactivation (PDI) represents a promising strategy to overcome bacterial resistance by combining light, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) that damage essential cellular components. Combining PDI with conventional antibiotics (ATBs) may further enhance bacterial eradication through complementary mechanisms. In this study, the tetracationic 5,10,15,20-tetra(4-N,N,Ntrimethylammoniophenyl)porphyrin (TMAP4+) was evaluated in combination with ATBs: ampicillin (AMP) and rifampicin (RIF) against Staphylococcus aureus and cephalexin (CFX) against Escherichia coli. The photostability of all agents was assessed under the experimental irradiation conditions, and no evidence of physical interaction between TMAP4+ and the ATBs was detected. AMP and CFX remained photostable, while RIF exhibited only minimal photodegradation under white light, confirming its stability during PDI treatments. The antimicrobial assays revealed that irradiation significantly enhanced the bactericidal activity of TMAP4+. When combined with ATBs, photoactivated TMAP4+ led to a pronounced reduction in the minimum inhibitory concentration (MIC) values of AMP and RIF for S. aureus and of CFX for E. coli, indicating additive effects. Growth curve analyses corroborated these results, showing delayed bacterial growth and decreased maximal optical densities in the combined treatments compared to single agents. Overall, these findings demonstrate that the photodynamic process can potentiate the antimicrobial effect of conventional ATBs without compromising their stability, supporting the potential of PS–ATB combination therapies as a valuable approach to improve antibacterial efficacy and mitigate ATB resistance.Fil: Acosta, Rocío Belén. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; ArgentinaFil: Durantini, Edgardo Néstor. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; ArgentinaFil: Spesia, Mariana Belen. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; ArgentinaMolecular Diversity Preservation International2025-11info: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/11336/281552Acosta, Rocío Belén; Durantini, Edgardo Néstor; Spesia, Mariana Belen; Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 23; 11-2025; 1-161422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/23/11267info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms262311267info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:30:09Zoai:ri.conicet.gov.ar:11336/281552instacron: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:34982026-02-26 10:30:09.906CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
title Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
spellingShingle Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
Acosta, Rocío Belén
PORPHYRIN
PHOTOSENSITIZER
PHOTOINACTIVATION
ANTIBIOTIC
title_short Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
title_full Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
title_fullStr Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
title_full_unstemmed Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
title_sort Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies
dc.creator.none.fl_str_mv Acosta, Rocío Belén
Durantini, Edgardo Néstor
Spesia, Mariana Belen
author Acosta, Rocío Belén
author_facet Acosta, Rocío Belén
Durantini, Edgardo Néstor
Spesia, Mariana Belen
author_role author
author2 Durantini, Edgardo Néstor
Spesia, Mariana Belen
author2_role author
author
dc.subject.none.fl_str_mv PORPHYRIN
PHOTOSENSITIZER
PHOTOINACTIVATION
ANTIBIOTIC
topic PORPHYRIN
PHOTOSENSITIZER
PHOTOINACTIVATION
ANTIBIOTIC
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Photodynamic inactivation (PDI) represents a promising strategy to overcome bacterial resistance by combining light, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) that damage essential cellular components. Combining PDI with conventional antibiotics (ATBs) may further enhance bacterial eradication through complementary mechanisms. In this study, the tetracationic 5,10,15,20-tetra(4-N,N,Ntrimethylammoniophenyl)porphyrin (TMAP4+) was evaluated in combination with ATBs: ampicillin (AMP) and rifampicin (RIF) against Staphylococcus aureus and cephalexin (CFX) against Escherichia coli. The photostability of all agents was assessed under the experimental irradiation conditions, and no evidence of physical interaction between TMAP4+ and the ATBs was detected. AMP and CFX remained photostable, while RIF exhibited only minimal photodegradation under white light, confirming its stability during PDI treatments. The antimicrobial assays revealed that irradiation significantly enhanced the bactericidal activity of TMAP4+. When combined with ATBs, photoactivated TMAP4+ led to a pronounced reduction in the minimum inhibitory concentration (MIC) values of AMP and RIF for S. aureus and of CFX for E. coli, indicating additive effects. Growth curve analyses corroborated these results, showing delayed bacterial growth and decreased maximal optical densities in the combined treatments compared to single agents. Overall, these findings demonstrate that the photodynamic process can potentiate the antimicrobial effect of conventional ATBs without compromising their stability, supporting the potential of PS–ATB combination therapies as a valuable approach to improve antibacterial efficacy and mitigate ATB resistance.
Fil: Acosta, Rocío Belén. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
Fil: Durantini, Edgardo Néstor. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
Fil: Spesia, Mariana Belen. Universidad Nacional de Río Cuarto. Instituto para el Desarrollo Agroindustrial y de la Salud. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto para el Desarrollo Agroindustrial y de la Salud; Argentina
description Photodynamic inactivation (PDI) represents a promising strategy to overcome bacterial resistance by combining light, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) that damage essential cellular components. Combining PDI with conventional antibiotics (ATBs) may further enhance bacterial eradication through complementary mechanisms. In this study, the tetracationic 5,10,15,20-tetra(4-N,N,Ntrimethylammoniophenyl)porphyrin (TMAP4+) was evaluated in combination with ATBs: ampicillin (AMP) and rifampicin (RIF) against Staphylococcus aureus and cephalexin (CFX) against Escherichia coli. The photostability of all agents was assessed under the experimental irradiation conditions, and no evidence of physical interaction between TMAP4+ and the ATBs was detected. AMP and CFX remained photostable, while RIF exhibited only minimal photodegradation under white light, confirming its stability during PDI treatments. The antimicrobial assays revealed that irradiation significantly enhanced the bactericidal activity of TMAP4+. When combined with ATBs, photoactivated TMAP4+ led to a pronounced reduction in the minimum inhibitory concentration (MIC) values of AMP and RIF for S. aureus and of CFX for E. coli, indicating additive effects. Growth curve analyses corroborated these results, showing delayed bacterial growth and decreased maximal optical densities in the combined treatments compared to single agents. Overall, these findings demonstrate that the photodynamic process can potentiate the antimicrobial effect of conventional ATBs without compromising their stability, supporting the potential of PS–ATB combination therapies as a valuable approach to improve antibacterial efficacy and mitigate ATB resistance.
publishDate 2025
dc.date.none.fl_str_mv 2025-11
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/11336/281552
Acosta, Rocío Belén; Durantini, Edgardo Néstor; Spesia, Mariana Belen; Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 23; 11-2025; 1-16
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/281552
identifier_str_mv Acosta, Rocío Belén; Durantini, Edgardo Néstor; Spesia, Mariana Belen; Photodynamic Inactivation Enhances Antibiotic Efficacy Without Affecting Drug Stability: Insights into Photosensitizer–Antibiotic Combination Therapies; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 23; 11-2025; 1-16
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/23/11267
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms262311267
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 Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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