Group photo. Pedro Garcia and Jesus Miguel Sanz
The activities of our laboratory have appeared twice in past editions of this publication, due to the double belonging to two groups: initially in June 2013 in the issue of "Biology of pathogenic microorganisms" (https://www.semicrobiologia.org /storage/secciones/publicaciones/semaforo/55/articulos/21_BMP_55_Garcia.pdf) and, later, in December 2014 in the special “Molecular Microbiology” (https://www.semicrobiologia.org/storage/secciones/publicaciones/ semaforo/58/articulos/43_MM22_PGarcia.pdf). Since then, the number of pre- and postdoctoral recruits has been reduced and, in addition, our boss Ernesto García has retired, who has become Professor Emeritus but continues to be a key player in our scientific development. On the other hand, the group of Dr. Jesús M. Sanz has recently been incorporated, which strengthens and complements our lines of research. The group belongs to CIBERES (CIBER of Respiratory Diseases), so the main focus of our research is on the study of antibacterial compounds against different pathogens that cause respiratory diseases. Traditionally, the target of our projects has been bacteria Streptococcus pneumoniae (pneumococcus), having addressed different topics: a) structural and functional analysis of PBCs ((pneumococcus), having addressed different topics: a) structural and functional analysis of PBCs ((pneumococcus), having addressed different topics: a) structural and functional analysis of PBCs (
At present, the fundamental lines of the laboratory converge in the use of protein structure and engineering techniques for the search and characterization of new antibacterial compounds that constitute alternative treatments against pathogens resistant to several antibiotics. The molecular nature of such compounds is broad, ranging from small organic molecules to complete enzymes (enzybiotics), and whose targets are also varied (cell membrane or wall), although they are always located on the bacterial surface.
In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens (Pseudomonas aeruginosa and In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens ( In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens (In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens (In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens (“In recent years we have developed small organic compounds (bicyclic amine esters or EBAs) that disrupt the cell membrane and have a lytic effect on both Gram-negative respiratory pathogens (” or CBRs). In both cases, the bactericidal effect is exponentially increased by the multivalent arrangement of several copies of these compounds in dendrimeric nanoparticles. On the other hand, endolysins are phage-encoded enzymes whose function is to hydrolyze the peptidoglycan of the host bacteria and finish the lytic cycle by disseminating new virions. In recent years, the use of a wide variety of endolysins against many bacterial pathogens has been described, which is a great hope for their future clinical application since they have several advantages over antibiotics. Among them we can mention: a) they are very specific; b) bacteria resistant to these enzymes have not been described, probably because their target (peptidoglycan) is a highly conserved structure among bacteria; c) for the same reason, they are equally effective against multiresistant strains; d) they also have bactericidal activity against bacteria that form biofilms that are generally refractory to antibiotics; e) are effective in all kinds of bacterial metabolic state. Also taking into account the numerous articles that have been published in recent years, it is clear that these antibacterials constitute a promising alternative to fight against the great threat of multi-resistant pathogens.
In addition, we have constructed the most potent chimeric enzymes against pneumococcus (Cpl-711 and PL3), strictly specific against this bacterium, but we have also characterized other endolysins with a broader host range, such as Cpl-7S and Csl2. Likewise, we have verified its synergistic action with certain antibiotics, or also between two enzybiotics that break different bonds. All of these enzymes have been shown to be highly effective against susceptible bacteria that form biofilms and have been validated in animal models, such as mice or zebrafish. In addition, we are studying new endolysins against Gram-negative pathogens, such as P. aeruginosa and In addition, we have constructed the most potent chimeric enzymes against pneumococcus (Cpl-711 and PL3), strictly specific against this bacterium, but we have also characterized other endolysins with a broader host range, such as Cpl-7S and Csl2. Likewise, we have verified its synergistic action with certain antibiotics, or also between two enzybiotics that break different bonds. All of these enzymes have been shown to be highly effective against susceptible bacteria that form biofilms and have been validated in animal models, such as mice or zebrafish. In addition, we are studying new endolysins against Gram-negative pathogens, such as.
At present, we are also investigating, alternatively, compounds that cause a non-lytic effect on bacteria, in such a way that the release of toxins and inflammatory factors into the medium is avoided while at the same time inducing the response of the host's defense system. In the case of pneumococcus, the addition of choline dendrimers or choline-binding modules (called CBMs) causes cell chaining and aggregation, leading to increased bacterial phagocytosis.
Finally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses.
Finally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses.
Finally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses.Finally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses. Streptococcus pneumoniaeFinally, we are introducing nanotechnology procedures in the laboratory for the multivalent immobilization of the aforementioned compounds on nanoparticles of a different chemical nature, with the ultimate goal of substantially increasing their activity, thus reducing the necessary doses.
effect on Gram-positiveeffect on Gram-positive Streptococcus pneumoniae effect on Gram-positive
effect on Gram-positive effect on Gram-positive
effect on Gram-positive effect on Gram-positive
Ferrándiz MJ, Cercenado MI, Domenech M, Tirado-Vélez JM, Escolano-Martínez MS, Yuste J, García E, de la Campa AG, Martín-Galiano AJ. Ferrándiz MJ, Cercenado MI, Domenech M, Tirado-Vélez JM, Escolano-Martínez MS, Yuste J, García E, de la Campa AG, Martín-Galiano AJ. Streptococcus pneumoniae in vitro Ferrándiz MJ, Cercenado MI, Domenech M, Tirado-Vélez JM, Escolano-Martínez MS, Yuste J, García E, de la Campa AG, Martín-Galiano AJ. https://www.omicsonline.org/open-access/autolysinindependent-dna-release-in-streptococcus-pneumoniae-invitro-biofilms.pdf.
Corsini B, Díez-Martínez R, Aguinagalde L, González-Camacho F, García-Fernández E, Letrado P, García P, Yuste J. Corsini B, Díez-Martínez R, Aguinagalde L, González-Camacho F, García-Fernández E, Letrado P, García P, Yuste J.