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| Página principal > Artículos > Artículos publicados > A Novel Generation of Tailored Antimicrobial Drugs Based on Recombinant Multidomain Proteins |
(Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí") (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia) (Institut de Ciència de Materials de Barcelona) (Institut de Ciència de Materials de Barcelona) (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT)) (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT)) (Universitat de Barcelona. Hospital Clínic. Servei de Malalties Infeccioses) (Institut de Recerca i Tecnologia Agroalimentàries) (Institut de Recerca i Tecnologia Agroalimentàries)
| Fecha: | 2023 |
| Resumen: | Antibiotic resistance has exponentially increased during the last years. It is necessary to develop new antimicrobial drugs to prevent and treat infectious diseases caused by multidrug- or extensively-drug resistant (MDR/XDR)-bacteria. Host Defense Peptides (HDPs) have a versatile role, acting as antimicrobial peptides and regulators of several innate immunity functions. The results shown by previous studies using synthetic HDPs are only the tip of the iceberg, since the synergistic potential of HDPs and their production as recombinant proteins are fields practically unexplored. The present study aims to move a step forward through the development of a new generation of tailored antimicrobials, using a rational design of recombinant multidomain proteins based on HDPs. This strategy is based on a two-phase process, starting with the construction of the first generation molecules using single HDPs and further selecting those HDPs with higher bactericidal efficiencies to be combined in the second generation of broad-spectrum antimicrobials. As a proof of concept, we have designed three new antimicrobials, named D5L37βD3, D5L37D5L37 and D5LAL37βD3. After an in-depth exploration, we found D5L37D5L37 to be the most promising one, since it was equally effective against four relevant pathogens in healthcare-associated infections, such as methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis (MRSE) and MDR Pseudomonas aeruginosa, being MRSA, MRSE and P. aeruginosa MDR strains. The low MIC values and versatile activity against planktonic and biofilm forms reinforce the use of this platform to isolate and produce unlimited HDP combinations as new antimicrobial drugs by effective means. |
| Ayudas: | Agencia Estatal de Investigación PID2019-107298RB-C21 Agencia Estatal de Investigación PID2019-105622RB-I00 Agencia Estatal de Investigación PID2020-115296RA-I00 Ministerio de Ciencia, Innovación y Universidades RYC-2017-22614 Fundació la Marató de TV3 201812-30-31-32-33 Ministerio de Ciencia e Innovación CEX2019-000917-S |
| Nota: | Altres ajuts: CERCA Programme/Generalitat de Catalunya; María Zambrano postdoctoral researcher contract (677904) from Ministerio de Universidades and European Union ("Financed by European Union-Next GenerationEU") |
| Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Lengua: | Anglès |
| Documento: | Article ; recerca ; Versió publicada |
| Materia: | Host defense peptides ; Antimicrobial ; Recombinant ; Nosocomial infections |
| Publicado en: | Pharmaceutics, Vol. 15, Issue 4 (April 2023) , art. 1068, ISSN 1999-4923 |
