Rv1268c protein peptide inhibiting Mycobacterium tuberculosis H37Rv entry to target cells

Tuberculosis (TB) remains one of the most worrying infectious diseases affecting public health around the world; 8.7 million new TB cases were reported in 2011. The search for an Mycobacterium tuberculosis H37Rv protein sequence which is functionally important in host-pathogen interaction has been proposed for developing a new vaccine which will allow efficient and safe control of the spread of this disease. The present study thus reports the results obtained for the Rv1268c protein described in the M. tuberculosis H37Rv genome as a hypothetical unknown, probably secreted, protein based on a highly robust, specific, sensitive and functional approach to the search for potential epitopes to be included in an anti-tuberculosis vaccine. Rv1268c presence was determined by immunoblotting after obtaining polyclonal sera against mycobacterial total sonicate or subcellular fractions. Such sera were used in electron immunomicroscopy (EIM) for confirming protein localisation on the M. tuberculosis envelop by recognising colloidal gold-labelled immunoglobulin. Screening assays revealed the presence of two sequences having high binding activity: one binding A549 alveolar epithelial cells ( 141TGMAALEQYLGSGHAVIVSI160) and other binding U937 monocyte-derived macrophages (21AVALGLASPADAAAGTMYGD40). Such sequences' ability to inhibit mycobacterial entry during in vitro assays was analysed. The structure of synthetic peptides binding to target cells was also determined, bearing in mind the structure-function relationship. These results, together with those obtained for other proteins, have been involved in selecting peptides which might be included in a subunit-based anti-tuberculosis vaccine. © 2013 Elsevier Ltd. All rights reserved.

• Fecha de publicación: 2013
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23554
• Acceso en línea: https://doi.org/10.1016/j.bmc.2013.08.018; https://repository.urosario.edu.co/handle/10336/23554
• Palabra clave: Bacterial protein; Protein rv1268c; Synthetic peptide; Unclassified drug; Animal experiment; Antibacterial activity; Article; Bacterial genome; Binding affinity; Cell invasion; Controlled study; Drug structure; Drug synthesis; In vitro study; Lung alveolus epithelium; Macrophage; Mycobacterium tuberculosis; Nonhuman; Protein localization; Rabbit; Structure activity relation; Target cell; Mycobacterium tuberculosis; Anti-tuberculosis vaccine; Entry inhibition; Receptor-ligand interaction; Rv1268c; Sub-cellular localization; Synthetic peptides; Target cell; Amino acid sequence; Animals; Bacterial proteins; Circular dichroism; Gold; Host-pathogen interactions; Humans; Immunoglobulins; Molecular sequence data; Mycobacterium tuberculosis; Peptides; Rabbits; Recombinant proteins; Anti-tuberculosis vaccine; Entry inhibition; Receptor-ligand interaction; Rv1268c; Sub-cellular localization; Synthetic peptides; Target cell; tumor; Cell line
• License: Abierto (Texto Completo)