Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Pneumococcal proteins involved in cell wall hydrolysis (CW hydrolases) are essential for cell expansion and division and contribute in different ways to pneumococcal virulence. In addition, the hydrolases encoded by pneumococcal bacteriophages have emerged as a promising alternative to antibiotics as new antimicrobials. In depth characterization of the bacterial and phage enzymes has provided the first complete structures and models of several family members, clues about substrate specificity and structural motifs recognized by their CW binding domains, and has demonstrated the relevance of modularity for activity. The design of mutants and/or chimeras with different selectivities or enhanced activities has thus been facilitated.
Project partners: Drs. P García and F Díaz (CIB-CSIC); JA Hermoso and M. Bruix (IQFR-CSIC).
Bustamante N, Iglesias-Bexiga M, Bernardo-García N, Silva-Martín N, García G, Campanero-Rhodes MA, García E, Usón I, Buey RM, García P, Hermoso JA, Bruix M, Menéndez M. 2017. Deciphering how Cpl-7 cell wall-binding repeats recognize the bacterial peptidoglycan. Sci Rep. 2017 Nov 28;7(1):16494. doi: 10.1038/s41598-017-16392-4. PMID: 29184076.
Rico-Lastres P, Díez-Martínez R, Iglesias-Bexiga M, Bustamante N, Aldridge C, Hesek D, Lee M, Mobashery S, Gray J, Vollmer W, García P, Menéndez M. 2015. Substrate recognition and catalysis by LytB, a pneumococcal peptidoglycan hydrolase involved in virulence. Sci. Rep., 5, 16198; doi: 10.1038/srep16198. PMID: 26537571
Bustamante N, Campillo NE, García E, Gallego C, Pera B, Diakun GP, Sáiz JL, García P, Díaz JF, Menéndez M. 2010. Cpl-7, a lysozyme encoded by a pneumococcal bacteriophage with a novel cell wall-binding motif. J Biol Chem 285: 33184-33196. PMID: 20720016
Hermoso JA, Lagartera L, González A, García P, Martínez-Ripoll M, García JL, Menéndez M. 2005. Crystal structure of the modular teichoic acid phosphorylcholine esterase Pce from Streptococcus pneumoniae: insights into the mechanism of bacterial pathogenesis. Nat Struct Mol Biol 12:533-538. PMID: 15895092
Bustamante N, Lastres P, García E, García P, Menéndez M. 2012. Thermal stability of Cpl-7 endolysin from the Streptococcus pneumoniae bacteriophage Cp-7; cell wall-targeting of its CW_7 motifs. Plos One 7, e46654. PMID: 23056389
Lorenzo-Díaz F, Dostal L, Coll M, Schildbach F, Menéndez M, Espinosa M. 2011. The MobM relaxase domain of plasmid pMV158: thermal stability and activity upon manganese and specific DNA binding. Nucl Acid Res 39: 4315-4329. PMID: 21296755
Monterroso B, Sáiz JL, García P, García JL, Menéndez M. 2008. Insights in structure and function relationships in pneumococcal cell-wall lysozymes: LytC and Cpl-1. J Biol Chem. 283: 2861-28628. PMID: 18667432
Martínez-Buey R, Monterroso B, Menéndez M, Diakun G, Chacón P, Hermoso JA., Díaz FJ. 2007. Insight into molecular plasticity of choline binding proteins (pneumococcal surface proteins) by SAXS. J Mol Biol. 365: 411-424. PMID: 17064729
Pérez-Dorado I, Campillo NE, Monterroso B, Hesek H, Lee M, Páez JA, García P, Martínez-Ripoll M, García JL, Mobashery S, Menéndez M, Hermoso J. 2007. Elucidation of the molecular recognition of the bacterial cell wall by modular phage pneumococcal endolysin Cpl-1. J Biol Chem. 282: 24990-24999. PMID: 17581815
Monterroso B, López-Zumel C, García JL, Sáiz JL, García P, Campillo NE, Menéndez, M. 2005. Unravelling the structure of pneumococcal autolytic lysozyme. Biochem J. 391: 41- 49. PMID: 15943581
Hermoso J, Monterroso B, Albert A, Galán B, Ahrazem O, García P, Martínez-Ripoll M, García JL, Menéndez M. 2003. Structural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1. Structure 11: 1239-1249
Varea J, Saiz JL, López Zumel C, Monterroso B, Iloro I, Arrondo JLR, Laynez J, García JL, Menéndez M. 2000. Do sequence repeats play an equivalent role in the choline-binding module of pneumococal LytA amidase? J Biol Chem. 275: 26842-26855
Varea J, Monterroso B, Saiz JL, López-Zumel C, García JL, Laynez J, García P, Menéndez M. 2004. Structural and thermodynamic characterization of Pal amidase, a phage lysin active against pneumococcus. J Biol Chem. 279: 43697-43707
Saiz JL,López Zumel C,Monterroso B, Arrondo JLR, Iloro I, Laynez J, García, JL, Menéndez M. 2002. Characterization of Ejl, the cell-wall amidase coded by pneumococcal bacteriophage Ej-1. Prot Sci. 11: 1788-1799
Usobiaga P, Medrano FJ, Gasset M, García JL, Saiz JL, Rivas G, Laynez J, Menéndez M. 1996. Structural organization of the major autolysin from Streptococcus pneumoniae. J Biol Chem. 271: 6832-6838
Medrano FJ, Gasset M, López-Zumel C, Usobiaga P, García, JL, Menéndez M. 1996. Structural characterization of the unligated and choline-bound LytA amidase: Conformational transitions induced by temperature. J Biol Chem. 271: 29152-29161