作者: Sudarvili Shanthalingam
DOI:
关键词: Binding site 、 Cytolysis 、 Microbiology 、 Pathogen 、 Receptor 、 Chemistry 、 Signal peptide 、 Lung injury 、 Peptide 、 Virulence factor
摘要: by Sudarvili Shanthalingam, Ph.D. Washington State University May 2010 Chair: Subramaniam Srikumaran Mannheimia haemolytica is the primary bacterial pathogen of bovine pneumonic pasteurellosis, an economically important disease cattle worldwide. Leukotoxin (Lkt) produced M. major virulence factor this organism. The cytolytic activity Lkt specific for ruminant leukocytes. utilizes CD18, β subunit β2-integrins, as its receptor on Previously, our laboratory mapped Lkt-binding domain to lie between amino acids (aa) 1-291 CD18. Therefore, next logical step was identify precise binding site within and determine whether co-administration CD18 peptide analogs would inhibit / mitigate haemolytica-caused lung injury. In study, using synthetic peptides spanning aa1-291 in Lkt-induced cytolysis assays, aa 5-17 Surprisingly, all belong predicted signal This observation led finding that not cleaved, intact renders ruminants susceptible Lkt. Site-directed mutagenesis a single resulted cleavage abrogation target cells. indicates engineering