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A Novel Generation of Tailored Antimicrobial Drugs Based on Recombinant Multidomain Proteins

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اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Contributors:
      Producció Animal; Producció de Remugants
    • بيانات النشر:
      MDPI
    • الموضوع:
      2023
    • Collection:
      IRTA Pubpro (Institute of Agrifood Research and Technology / Institut de Recerca i Tecnologia Agroalimentàries)
    • الموضوع:
      577
    • نبذة مختصرة :
      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. ; info:eu-repo/semantics/publishedVersion
    • File Description:
      application/pdf
    • ISSN:
      1999-4923
    • Relation:
      Pharmaceutics; MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-107298RB-C21/ES/PRODUCCION Y VALIDACION DE FARMACOS BASADOS EN PEPTIDOS DE DEFENSA DEL HUESPED PARA EL TRATAMIENTO DEL SINDROME RESPIRATORIO BOVINO/; MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-105622RB-I00/ES/PROCESAMIENTO DE MOLECULAS PARA CREAR MATERIALES HIBRIDOS ESTRUCTURADOS JERARQUICAMENTE PARA APLICACIONES BIOMEDICAS/; MINECO/Programa Estatal de promoción del talento y su empleabilidad en I+D+I/RYC-2017-22614/ES/ /; MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-115296RA-I00/ES/MIMETIZANDO EL SISTEMA INMUNITARIO CONTRA EL CANCER/; MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/CEX2019-000917-S/ES/ /; López-Cano, Adrià, Neus Ferrer-Miralles, Julieta Sánchez, Jose Vicente Carratalá, Xavier Rodriguez Rodriguez, Imma Ratera, and Judith Guasch et al. 2023. "A Novel Generation Of Tailored Antimicrobial Drugs Based On Recombinant Multidomain Proteins". Pharmaceutics 15 (4): 1068. doi:10.3390/pharmaceutics15041068.; http://hdl.handle.net/20.500.12327/2222; https://doi.org/10.3390/pharmaceutics15041068
    • الرقم المعرف:
      10.3390/pharmaceutics15041068
    • Rights:
      Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ ; info:eu-repo/semantics/openAccess
    • الرقم المعرف:
      edsbas.7DDBE098