tailieunhanh - Báo cáo khoa học: Inhibition of pneumococcal choline-binding proteins and cell growth by esters of bicyclic amines

Streptococcus pneumoniaeis one of the major pathogens worldwide. The use of currently available antibiotics to treat pneumococcal diseases is ham-pered by increasing resistance levels; also, capsular polysaccharide-based vaccination is of limited efficacy. Therefore, it is desirable to find targets for the development of new antimicrobial drugs specifically designed to fight pneumococcal infections. | ễFEBS Journal Inhibition of pneumococcal choline-binding proteins and cell growth by esters of bicyclic amines Beatriz Maestro1 Ana Gonzalez2 Pedro García2 and Jesus M. Sanz1 1 Institute de Biologia Molecular y Celular Universidad MiguelHernandez Elche Spain 2 Departamento de Microbiologia Molecular Centro de Investigaciones Biologicas Consejo Superior de Investigaciones Cientificas Madrid Spain Keywords antibiotic resistance circular dichroism CD inhibition of bacterialgrowth repeat proteins Streptococcus pneumoniae Correspondence B. Maestro Instituto de Biologia Molecular y Celular Universidad MiguelHernandez Edificio Torregaitan Avda Universidad s n Elche E-O32o2 Spain Fax 34 966 658 758 Tel 34 966 658 474 E-mail bmaestro@ Received 18 October 2006 revised 6 November 2006 accepted 9 November 2006 doi Streptococcus pneumoniae is one of the major pathogens worldwide. The use of currently available antibiotics to treat pneumococcal diseases is hampered by increasing resistance levels also capsular polysaccharide-based vaccination is of limited efficacy. Therefore it is desirable to find targets for the development of new antimicrobial drugs specifically designed to fight pneumococcal infections. Choline-binding proteins are a family of polypeptides found in all S. pneumoniae strains that take part in important physiologic processes of this bacterium. Among them are several murein hydrolases whose enzymatic activity is usually inhibited by an excess of choline. Using a simple chromatographic procedure we have identified several choline analogs able to strongly interact with the choline-binding module C-LytA of the major autolysin of S. pneumoniae. Two of these compounds atropine and ipratropium display a higher binding affinity to C-LytA than choline and also increase the stability of the protein. CD and fluorescence spectroscopy analyses revealed that the conformational changes of C-LytA upon binding of these alkaloids are .