Alpha hemolysin polymorphisms in methicillin-resistant Staphylococcus aureus clinical isolates regulate ADAM10-dependent neutrophil IL-1 beta secretion
Liboro, K.; Chau, J. T.; Begando, J.; Abbodante, S.; Lackner, A.; Marshall, M. E.; Sun, Y.; Ly, N.; Dubyak, G. R.; Gilmore, M.; McNulty, R.; Andre, C.; Pearlman, E. S.
Show abstract
Staphylococcus aureus -hemolysin (Hla) is a major virulence factor that utilizes cell surface ADAM10 to oligomerize and form a functional heptameric pore. We show here that Hla from strain USA300 is required to induce IL-1{beta} secretion by neutrophils and to cause severe corneal disease in mice. We also demonstrate that in contrast to USA300 and other clonal complex 8 (CC8) methicillin resistant S. aureus (MRSA) isolated from the skin, CC5 Hla from corneas of infected patients have single nucleotide polymorphisms (SNP) that result in two amino acid substitutions, D208E (Asp-Glu) and I275T (Ile-Thr). Structural modeling predicts CC5 Hla self-assembly and altered binding to ADAM10 that is distinct from CC8 Hla. The ADAM10 inhibitor GI254023X blocked neutrophil IL-1{beta} secretion induced by Hla-expressing CC8, but not by CC5 conditioned media, indicating that these Hla polymorphisms play an important role in Hla receptor binding and neutrophil IL-1{beta} secretion, and affect corneal disease severity.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Neisseria gonorrhoeae co-opts C4b-binding protein to enhance complement-independent survival from neutrophils 95%
- Uncovering the neutrophil inflammatory response in severe COVID-19: implications of type I interferon in inflammasome activation 94%
- A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence 94%
Similar papers in this journal
- Collagen binding adhesin restricts Staphylococcus aureus skin infection 95%
- A Two-Step Activation Mechanism Enables Mast Cells to Differentiate their Response between Extracellular and Invasive Enterobacterial Infection 95%
- Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.