Searching for Antipneumococcal Targets: Choline-Binding Modules as Phagocytosis Enhancers.

ACS Infectious Diseases
Emma Roig-MolinaBeatriz Maestro

Abstract

Choline-binding proteins (CBPs) from Streptococcus pneumoniae comprise a family of modular polypeptides involved in essential events of this pathogen. They recognize the choline residues present in the teichoic and lipoteichoic acids of the cell wall using the so-called choline-binding modules (CBMs). The importance of CBPs in pneumococcal physiology points to them as novel targets to combat antimicrobial resistances shown by this organism. In this work we have tested the ability of exogenously added CBMs to act as CBP inhibitors by competing with the latter for the binding to the choline molecules in the bacterial surface. First, we carried out a thorough physicochemical characterization of three native CBMs, namely C-LytA, C-Cpl1, and C-CbpD, and assessed their affinity for choline and macromolecular, pneumococcal cell-wall mimics. The interaction with these substrates was evaluated by molecular modeling, analytical ultracentrifugation, surface plasmon resonance, and fluorescence and circular dichroism spectroscopies. Van't Hoff thermal analyses unveiled the existence of one noncanonical choline binding site in each of the C-Cpl1 and C-CbpD proteins, leading in total to 5 ligand-binding sites per dimer and 4 sites per monomer...Continue Reading

References

Jan 15, 1992·European Journal of Biochemistry·J M Sanchez-PuellesE Garcia
Jan 1, 1990·Annual Review of Biophysics and Biophysical Chemistry·E FreireJ M Sanchez-Ruiz
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·E GarcíaR López
Jan 15, 1985·European Journal of Biochemistry·T Briese, R Hakenbeck
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R Brent, M Ptashne
Jul 1, 1994·Journal of Bacteriology·J L GarciaP Garcia
Oct 1, 1995·Protein Science : a Publication of the Protein Society·J K MyersJ M Scholtz
Mar 22, 1996·The Journal of Biological Chemistry·P UsobiagaM Menéndez
Jul 1, 1997·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·R LópezJ L García
Jun 13, 2000·The Journal of Biological Chemistry·J VareaM Menéndez
Sep 19, 2000·Infection and Immunity·K K GosinkH R Masure
Sep 7, 2001·Journal of Bacteriology·J HoskinsJ I Glass
Nov 6, 2001·Nature Structural Biology·C Fernández-TorneroA Romero
Apr 22, 1960·Biochimica Et Biophysica Acta·S LACKS, R D HOTCHKISS
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jun 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sébastien GuiralJean-Pierre Claverys
Oct 27, 2006·Journal of Molecular Biology·Rubén M BueyJ Fernando Díaz
Aug 1, 2008·The Journal of Biological Chemistry·Begoña MonterrosoMargarita Menéndez
Sep 16, 2008·Journal of Chromatography. a·Beatriz MaestroJesús M Sanz
Dec 31, 2008·Angewandte Chemie·Víctor M Hernández-RocamoraJesús M Sanz
Sep 15, 2009·Lancet·Katherine L O'BrienUNKNOWN Hib and Pneumococcal Global Burden of Disease Study Team
Oct 1, 1915·The Journal of Experimental Medicine·C G Bull
Apr 20, 2010·Nature Structural & Molecular Biology·Inmaculada Pérez-DoradoJuan A Hermoso
Jun 1, 2011·Nucleic Acids Research·Aurélien GrosdidierOlivier Michielin
Jul 5, 2012·Molecular Oral Microbiology·I Pérez-DoradoJ A Hermoso
Sep 7, 2012·Angewandte Chemie·Carlo FastingRainer Haag
Sep 8, 2012·BMC Infectious Diseases·Catherine Weil-OlivierLorenzo Mantovani

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