title: Two human host defense ribonucleases against mycobacteria, the eosinophil cationic protein (RNase 3) and RNase 7.
abstract: There is an urgent need to develop new agents against mycobacterial infections, such as tuberculosis and other respiratory tract or skin affections. In this study, we have tested two human antimicrobial RNases against mycobacteria. RNase 3, also called the eosinophil cationic protein, and RNase 7 are two small cationic proteins secreted by innate cells during host defense. Both proteins are induced upon infection displaying a wide range of antipathogen activities. In particular, they are released by leukocytes and epithelial cells, contributing to tissue protection. Here, the two RNases have been proven effective against Mycobacterium vaccae at a low micromolar level. High bactericidal activity correlated with their bacterial membrane depolarization and permeabilization activities. Further analysis on both protein-derived peptides identified for RNase 3 an N-terminus fragment that is even more active than the parental protein. Also, a potent bacterial agglutinating activity was unique to RNase 3 and its derived peptide. The particular biophysical properties of the RNase 3 active peptide are envisaged as a suitable reference for the development of novel antimycobacterial drugs. The results support the contribution of secreted RNases to the host immune response against mycobacteria.
authors.affiliation: Department of Biochemistry and Molecular Biology, Biosciences Faculty, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pulido
authors.forename: Marc
authors.initials: M
authors.lastname: Torrent
authors.forename: David
authors.initials: D
authors.lastname: Andreu
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Nogués
authors.forename: Ester
authors.initials: E
authors.lastname: Boix
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability; D004789:Enzyme Activation; D047150:Eosinophil Cationic Protein / Q000138:chemical synthesis / Q000494:pharmacology*; D005813:Genes, Synthetic; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D012260:Ribonucleases / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D011994:Recombinant Proteins; D012260:Ribonucleases; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; C470000:Ribonuclease 7