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http://hdl.handle.net/2445/191021
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DC Field | Value | Language |
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dc.contributor.author | Ratia, Carlos | - |
dc.contributor.author | Cepas, Virginio | - |
dc.contributor.author | Soengas, Raquel | - |
dc.contributor.author | Navarro, Yolanda | - |
dc.contributor.author | Velasco de Andrés, María | - |
dc.contributor.author | Iglesias, Maria José | - |
dc.contributor.author | Lozano Soto, Francisco | - |
dc.contributor.author | López Ortiz, Fernando | - |
dc.contributor.author | Soto, Sara M. | - |
dc.date.accessioned | 2022-11-21T16:30:53Z | - |
dc.date.available | 2022-11-21T16:30:53Z | - |
dc.date.issued | 2022-03-03 | - |
dc.identifier.issn | 1664-302X | - |
dc.identifier.uri | http://hdl.handle.net/2445/191021 | - |
dc.description.abstract | The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 μM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents. | - |
dc.format.extent | 20 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fmicb.2022.815622 | - |
dc.relation.ispartof | Frontiers in Microbiology, 2022, vol. 13 | - |
dc.relation.uri | https://doi.org/10.3389/fmicb.2022.815622 | - |
dc.rights | cc-by (c) Ratia, Carlos et al., 2022 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Resistència als medicaments | - |
dc.subject.classification | Medicaments antibacterians | - |
dc.subject.classification | Crisoteràpia | - |
dc.subject.other | Drug resistance | - |
dc.subject.other | Antibacterial agents | - |
dc.subject.other | Chrysotherapy | - |
dc.title | A C˄S-cyclometallated gold(III) complex as novel antibacterial candidate against drug-resistant bacteria | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 718500 | - |
dc.date.updated | 2022-11-21T16:30:53Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.idimarina | 9301695 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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718500.pdf | 5.88 MB | Adobe PDF | View/Open |
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