Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae
Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223007394 |
| _version_ | 1797801825116618752 |
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| author | Dafne Berenice Hormazábal Ángeles Beatriz Reyes Francisco Castro Alan R. Cabrera Paulina Dreyse Felipe Melo-González Susan M. Bueno Iván A. González Christian Erick Palavecino |
| author_facet | Dafne Berenice Hormazábal Ángeles Beatriz Reyes Francisco Castro Alan R. Cabrera Paulina Dreyse Felipe Melo-González Susan M. Bueno Iván A. González Christian Erick Palavecino |
| author_sort | Dafne Berenice Hormazábal |
| collection | DOAJ |
| description | Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen species. We test Ru-based PS to inhibit K. pneumoniae and advance in the characterization of the mode of action. The PDI activity of PSRu-L2, and PSRu-L3, was determined by serial micro dilutions exposing K. pneumoniae to 0.612 J/cm 2 of light dose. PS interaction with cefotaxime was determined on a collection of 118 clinical isolates of K. pneumoniae. To characterize the mode of action of PDI, the bacterial response to oxidative stress was measured by RT-qPCR. Also, the cytotoxicity on mammalian cells was assessed by trypan blue exclusion. Over clinical isolates, the compounds are bactericidal, at doses of 8 µg/mL PSRu-L2 and 4 µg/mL PSRu-L3, inhibit bacterial growth by 3 log10 (>99.9%) with a lethality of 30 min. A remarkable synergistic effect of the PSRu-L2 and PSRu-L3 compounds with cefotaxime increased the bactericidal effect in a subpopulation of 66 ESBL-clinical isolates to > 6 log10 with an FIC-value of 0.16 and 0.17, respectively. The bacterial transcription response suggests that the mode of action occurs through Type II oxidative stress. The upregulation of the extracytoplasmic virulence factors mrkD, magA, and rmpA accompanied this response. Also, the compounds show little or no toxicity in vitro on HEp-2 and HEK293T cells. Through the type II effect, PSs compounds are bactericidal, synergistic on K. pneumoniae, and have low cytotoxicity in mammals. |
| first_indexed | 2024-03-13T04:56:25Z |
| format | Article |
| id | doaj.art-2452e0c9c6af494986665190c87a0da1 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-13T04:56:25Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
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| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-2452e0c9c6af494986665190c87a0da12023-06-18T05:00:48ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-08-01164114949Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniaeDafne Berenice Hormazábal0Ángeles Beatriz Reyes1Francisco Castro2Alan R. Cabrera3Paulina Dreyse4Felipe Melo-González5Susan M. Bueno6Iván A. González7Christian Erick Palavecino8Laboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, ChileLaboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, ChileDepartamento de Química Inorgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Macul, Santiago, ChileDepartamento de Química Inorgánica, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Macul, Santiago, ChileDepartamento de Química, Universidad Técnica Federico Santa María, Av. España 1680, Casilla 2390123, Valparaíso, ChileMillennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, ChileMillennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, ChileDepartamento de Química, Facultad de Ciencias Naturales, Matemática y del Medio Ambiente, Universidad Tecnológica Metropolitana, Las Palmeras 3360, Ñuñoa, Santiago 7800003, Chile; Corresponding authors.Laboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Lord Cochrane 418, Santiago 8330546, Chile; Corresponding authors.Multidrug-resistant bacteria, such as ESBL producing-Klebsiella pneumoniae, have increased substantially, encouraging the development of complementary therapies such as photodynamic inactivation (PDI). PDI uses photosensitizer (PS) compounds that kill bacteria using light to produce reactive oxygen species. We test Ru-based PS to inhibit K. pneumoniae and advance in the characterization of the mode of action. The PDI activity of PSRu-L2, and PSRu-L3, was determined by serial micro dilutions exposing K. pneumoniae to 0.612 J/cm 2 of light dose. PS interaction with cefotaxime was determined on a collection of 118 clinical isolates of K. pneumoniae. To characterize the mode of action of PDI, the bacterial response to oxidative stress was measured by RT-qPCR. Also, the cytotoxicity on mammalian cells was assessed by trypan blue exclusion. Over clinical isolates, the compounds are bactericidal, at doses of 8 µg/mL PSRu-L2 and 4 µg/mL PSRu-L3, inhibit bacterial growth by 3 log10 (>99.9%) with a lethality of 30 min. A remarkable synergistic effect of the PSRu-L2 and PSRu-L3 compounds with cefotaxime increased the bactericidal effect in a subpopulation of 66 ESBL-clinical isolates to > 6 log10 with an FIC-value of 0.16 and 0.17, respectively. The bacterial transcription response suggests that the mode of action occurs through Type II oxidative stress. The upregulation of the extracytoplasmic virulence factors mrkD, magA, and rmpA accompanied this response. Also, the compounds show little or no toxicity in vitro on HEp-2 and HEK293T cells. Through the type II effect, PSs compounds are bactericidal, synergistic on K. pneumoniae, and have low cytotoxicity in mammals.http://www.sciencedirect.com/science/article/pii/S0753332223007394MDR bacteriaMode of actionComplementary therapies, 6 log10 inhibition |
| spellingShingle | Dafne Berenice Hormazábal Ángeles Beatriz Reyes Francisco Castro Alan R. Cabrera Paulina Dreyse Felipe Melo-González Susan M. Bueno Iván A. González Christian Erick Palavecino Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae Biomedicine & Pharmacotherapy MDR bacteria Mode of action Complementary therapies, 6 log10 inhibition |
| title | Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae |
| title_full | Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae |
| title_fullStr | Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae |
| title_full_unstemmed | Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae |
| title_short | Synergistic effect of Ru(II)-based type II photodynamic therapy with cefotaxime on clinical isolates of ESBL-producing Klebsiella pneumoniae |
| title_sort | synergistic effect of ru ii based type ii photodynamic therapy with cefotaxime on clinical isolates of esbl producing klebsiella pneumoniae |
| topic | MDR bacteria Mode of action Complementary therapies, 6 log10 inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223007394 |
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