English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/163820
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE   Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

Engineering Salmonella as intracellular factory for effective killing of tumour cells

AutorCamacho, Eva María ; Mesa-Pereira, Beatriz ; Medina, Carlos ; Flores, Amando ; Santero, Eduardo
Palabras claveCp53
Delivery
Apoptosis
Autolysis
Salmonella
Tumour
Fecha de publicación2016
CitaciónBio.Iberoamérica 2016
Resumen[Background]: The use of bacteria as factories for therapeutic proteins production in vivo is a promising biomedical tool. Especially, live bacteria therapy is viewed as an alternative in cancer treatment due to the capacity of several species to target and penetrate tumours. Salmonella, in addition to having this capability, can be easily engineered to produce antitumor molecules from inside the tumour, thus increasing the specificity and efficiency of the treatments. One of the main limitations of this approach is the efficient release of therapeutic molecules from intratumoral bacteria. [Results]: In this study we have developed an inducible autolysis system that, in response to anhydrotetracycline, lysates intracellular bacteria releasing their content. The lysis operon of lambda phage was cloned under the Ptet promoter control into modified vectors and introduced into Salmonella strains. The system was combined with a salicylate cascade system that allows efficient production of the therapeutic molecules in response to aspirin. This strain was further modified introducing a sifA mutation into the bacterial chromosome that liberates bacteria from the vacuoles to a cytosolic location. Our results show that almost 100% of the bacterial population die after lysis induction both in bacterial and cellular cultures. This bacterial lysis correlates with the release of bacterial content into the growth media or cytosol, respectively. We have used our engineered strain for the intracellular production and delivery of Cp53 peptide. The results indicate that when production and release of this peptide are suitably separated in the time, the Cp53 peptide produced intracellularly induces cell death. [Conclusion]: The combination of three elements – namely, an aspirin inducible system for therapeutic molecules production, an anhydrotetracycline inducible system for bacterial content release and a sifA mutation – makes our strain a putative powerful instrument in cancer treatment. The engineered strain is able to produce and release cytotoxic peptides while it proliferates inside tumour cells, thus inducing host cell death. Our results show that temporal separation of protein production from protein release is essential to kill efficiently tumour cells. The combined system is a step further in the engineering of the perfect bacteria for cancer therapy.
DescripciónResumen del trabajo presentado al 1er Congreso Iberoamericano de Biotecnología: "Bio.Iberoamérica 2016. Biotecnología Integrando Continentes”, celebrado en Salamanca (España) entre el 5 y el 8 de junio de 2016.
URIhttp://hdl.handle.net/10261/163820
Aparece en las colecciones: (CABD) Comunicaciones congresos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.