Lysostaphin expression in mammary glands confers protection against staphylococcal infection in transgenic mice
| Autor: | Karen Plaut, A. J. Bramley, C. M. Williamson, Kevin D. Wells, David Kerr, Alistair J. Lax, Robert J. Wall, K Moore |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Genetically modified mouse
Ratón Glutamine Staphylococcus Mammary gland Biomedical Engineering Bioengineering Mice Transgenic Biology medicine.disease_cause Applied Microbiology and Biotechnology Microbiology Mice Mammary Glands Animal stomatognathic system Gene expression medicine Animals Lactation Secretion Mastitis Bovine Antibacterial agent Lysostaphin Lysine Staphylococcal Infections Recombinant Proteins medicine.anatomical_structure Milk Amino Acid Substitution Staphylococcus aureus Molecular Medicine Cattle Female Asparagine Genetic Engineering Biotechnology |
| Zdroj: | Nature biotechnology. 19(1) |
| ISSN: | 1087-0156 |
| Popis: | Infection of the mammary gland, in addition to causing animal distress, is a major economic burden of the dairy industry. Staphylococcus aureus is the major contagious mastitis pathogen, accounting for approximately 15-30% of infections, and has proved difficult to control using standard management practices. As a first step toward enhancing mastitis resistance of dairy animals, we report the generation of transgenic mice that secrete a potent anti-staphylococcal protein into milk. The protein, lysostaphin, is a peptidoglycan hydrolase normally produced by Staphylococcus simulans. When the native form is secreted by transfected eukaryotic cells it becomes glycosylated and inactive. However, removal of two glycosylation motifs through engineering asparagine to glutamine codon substitutions enables secretion of Gln(125,232)-lysostaphin, a bioactive variant. Three lines of transgenic mice, in which the 5'-flanking region of the ovine beta-lactoglobulin gene directed the secretion of Gln(125,232)-lysostaphin into milk, exhibit substantial resistance to an intramammary challenge of 104 colony-forming units (c.f.u.) of S. aureus, with the highest expressing line being completely resistant. Milk protein content and profiles of transgenic and nontransgenic mice are similar. These results clearly demonstrate the potential of genetic engineering to combat the most prevalent disease of dairy cattle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|