Group members (left to right): Andrea Flores, Mercedes Spínola, Federico M. Ruiz, Elena Santillana, Irene Davó, Antonio Romero and Javier Medrano.
Infectious diseases are the leading cause of death worldwide and are a major challenge for public health. Despite recent advances in biochemical and structural studies of a series of pathogenic factors, a better understanding of targets involved in antibiotic resistance and microbial pathogenesis and how they are transferred is important to combat infectious diseases. Approaches to combat bacterial infection rely on, 1) the disruption of the bacteria growth cycle by preventing the synthesis and assembly of key components of bacterial processes and, 2) by inhibition of virulence traits.
Our goal is to better understand the pathogenic mechanisms developed by gram-negative organisms (A. baumannii, P. aeruginosa, ..) in infection, using a structural approach.
MAIN RESEARCH LINES
1. β-lactamases and bacterial toxin-antitoxin systems. The number of class D carbapenemases identified in hospitals worldwide continues to grow significantly. Most of them have been isolated from gram-negative pathogens. Our more recent efforts attempt to correlate resistance mutations in new subfamilies of oxacillinases for the design of new antimicrobial agents.
Furthermore, we are focusing in the structural characterization of the AbkA/AbkB toxin-antitoxin system in A. baumannii, related to virulence and involved in the successful dissemination of plasmids carrying the blaOXA-24/40-like gene, thus contributing to the plasmid stability.
2. Type VI secretion system (T6SS). Due to the difficulties inherent to this system, we have designed a strategy to address each individual component and subsequent assembly in silico. We have solved the crystal structure of Hcp (TssD) of A. baumannii characterizing the aggregation state by electron microscopy. Policlonal antibodies against Hcp confirmed that the T6SS of A. baumannii is active and functional in the AB0057 strain and in other different nosocomial strains of diverse origins. Very recently, we reported the crystal structure of VgrG1 from P. aeruginosa. Our study reveals several remarkable structural features pointing to the possible roles of the two main segments of VgrG1: the head as a scaffold cargo domain and the β-roll spike with implications in the cell-membrane puncturing process and as a carrier of cognate toxins.
Spínola-Amilibia M., Davó-Siguero I., Ruiz F.M., Santillana E., Medrano F.J., Romero A . The structure of VgrG1 from Pseudomonas aeruginosa, the needle tip of the bacterial Type VI Secretion System. Acta Cryst D72, 22-33
Solís D., Bovin N.V., Davis A.P., Jiménez-Barbero J., Romero A., Roy R., Smetana K. Jr., Gabius H.-J. . A guide into glycosciences: How chemistry, biochemistry and biology cooperate to crack the sugar code. Biochim. Biophys. Acta 1850, 186-235 doi:10.1016/j.bbagen.2014.03.016
Flores-Ibarra A., Ruiz F.M., André S., Gabius H.-J., Romero A. . Preliminary X-ray crystallographic analysis of an engineered variant of human chimera-type galectin-3 with a shortened N-terminal domain. Acta Cryst. F71, 184-188
Linde D., Pogni R., Canellas M., Lucas F., Guallar V., Baratto M.C., Sinicropi A., Sáez-Jiménez V., Coscolin C., Romero A., Medrano F.J., Ruiz-Dueñas F.J., Martinez A.T. . Catalytic surface radical in dye-decolorizing peroxidase: A computational, spectroscopic and site-directed mutagenesis study. Biochem. J. 466, 253-262, doi:10.1042/BJ20141211
Ruiz-Arellano R.R., Medrano F.J., Moreno A., Romero A. . Crystal Structure of struthiocalcin-1, an intramineral protein from Struthio camelus eggshell, in two crystal forms. Acta Cryst. D71, 809-818
Ruiz F.M., Santillana E., Spínola-Amilibia M., Torreira E., Culebras E., Romero A. . Crystal structure of Hcp from Acinetobacter baumannii: a component of the Type VI Secretion System. PLoS One 10(6): e0129691 | DOI:10.1371/journal.pone.0129691
Ruiz F.M., Gilles U., Lindner I., André S., Romero A., Reusch D. Gabius H.-J. . Combining Crystallography and Hydrogen/Deuterium Exchange to Study Galectin-Ligand Complexes. Chem. Eur. J. 21, 13558-13568
Sáez-Jiménez V., Fernández-Fueyo E., Medrano F.J., Romero A., Martínez A.T., Ruiz-Dueñas F.J. . Improving the pH-stability of Versatile Peroxidase by Comparative Structural Analysis with a Naturally-stable Manganese Peroxidase. PLoS One 10(10): DOI:10.1371/journal.pone.0140984
Ruiz, F.M., Scholz, B.A., Buzamet, E., Kopitz, J., André, S.*, Menéndez, M., Romero, A.*, Solís, D.*, Gabius, H.-J. . Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells. FEBS J. (2014) 281, 1446-1464
Fernández-Fueyo, E., Ruiz-Dueñas, F.J., Martínez, M.J., Romero, A., Hammel, K.E., Medrano, F.J., Martínez, A.T. . Ligninolytic peroxidase genes in the oyster mushroom genome: heterologous expression, molecular structure, catalytic and stability properties, and lignin-degrading ability. Biotechnol. Biofuels. (2014) 7:2 doi:10.1186/1754-6834-7-2
MINECO (BFU2014-55448-P) (2015-2016)
CM S2010/BMD2353 (2012-2016)
MICINN (BFU2011-24615) (2011-2014)
MICINN CONSOLIDER-INGENIO (CSD2009-00088) (2011-2016)