Understanding Pathogen Biology - Key New Therapies

Explore a comprehensive lecture on pathogen biology and emerging therapeutic approaches in "Understanding Pathogen Biology: Key New Therapies." Delve into the complexities of human sepsis pathogens and their toxins, focusing on Staphylococcus aureus α-toxin (Hla) and its role in sepsis. Examine the anatomy of pathogens and the intricacies of virulence. Learn about A Disintegrin and Metalloprotease 10 (ADAM10) as the cellular receptor for Hla and its impact on endothelial barriers and platelet function. Investigate host responses to endothelial injury and the effects of platelet ADAM10 knockout on sepsis-associated lung injury. Analyze the relationship between platelet sensitivity to Hla and neutrophil inflammatory cytokine production. Discover how platelet-myeloid double ADAM10 knockout protects against multi-organ injury in sepsis and its association with survival rates. Explore the temporo-spatial action of Hla in sepsis and evaluate the potential of highly targeted therapeutic approaches. Conclude with a proposed model for focused interventions in sepsis treatment.

Intro
Disclosure
Human sepsis pathogens and their toxins
Anatomy of a pathogen: complexity of virulence
Staphylococcus aureus a-toxin (Hla) in sepsis
A Disintegrin and Metalloprotease 10 (ADAM10) is the cellular receptor for Hla
Hla injures the endothelial barrier
Host response to endothelial injury
Hla utilizes ADAM 10 to block platelet function
Platelet ADAM 10 knockout mitigates sepsis- associated lung injury
Platelet sensitivity to Hla enhances neutrophil inflammatory cytokine production
Platelet-myeloid double ADAM 10 knockout protects against multi-organ injury in sepsis
Protection against multi-organ toxin injury is associated with sepsis survival
Temporo-spatial action of Hla in sepsis
Can highly targeted approaches be successful?
A proposed model for focused interventions
Acknowledgements