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Published on: May 4, 2018
Bovine NK-lysin-derived peptides have bactericidal effects against Mycobacterium avium subspecies paratuberculosis
Rohana P Dassanayake1, Taylor L T Wherry2,3, Shollie M Falkenberg4
1Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA. rohana.dassanayake@usda.gov.
Abstract:
Infection with Mycobacterium avium subspecies paratuberculosis (MAP) is complex, but little is known about the role that natural killer (NK) cells play. In the present study, four bovine NK-lysin peptides were synthesized to evaluate their bactericidal activity against MAP. The results demonstrated that bNK-lysin peptides were directly bactericidal against MAP, with bNK1 and bNK2A being more potent than bNK2B and bNK2C. Mechanistically, transmission electron microscopy revealed that the incubation of MAP with bNK2A resulted in extensive damage to cell membranes and cytosolic content leakage. Furthermore, the addition of bNK2A linked with a cell-penetrating peptide resulted in increased MAP killing in a macrophage model.
Insights
Bovine NK-lysin peptides show direct bactericidal activity against Mycobacterium avium subspecies paratuberculosis (MAP). These peptides, particularly bNK1 and bNK2A, damage MAP cell membranes, offering potential therapeutic strategies for MAP infections.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Mycobacterium avium subspecies paratuberculosis (MAP) causes complex infections.
- The role of natural killer (NK) cells in MAP infections is not well understood.
Purpose of the Study:
- To synthesize and evaluate the bactericidal activity of bovine NK-lysin peptides against MAP.
- To investigate the mechanism of action of these peptides on MAP.
Main Methods:
- Synthesis of four bovine NK-lysin peptides.
- Assessment of direct bactericidal activity against MAP.
- Transmission electron microscopy to visualize cellular damage.
- Macrophage model with cell-penetrating peptide conjugation.
Main Results:
- Bovine NK-lysin peptides demonstrated direct bactericidal effects on MAP.
- bNK1 and bNK2A exhibited greater potency than bNK2B and bNK2C.
- bNK2A induced significant cell membrane damage and cytosolic leakage in MAP.
- Enhanced MAP killing was observed when bNK2A was linked to a cell-penetrating peptide in macrophages.
Conclusions:
- Bovine NK-lysin peptides possess direct bactericidal properties against MAP.
- The peptides, especially bNK2A, disrupt MAP cell integrity.
- Cell-penetrating peptide conjugation enhances the efficacy of bNK2A in a macrophage model, suggesting therapeutic potential.
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