Bi-component HlgC/HlgB and HlgA/HlgB γ-hemolysins from S. aureus: Modulation of Ca2+ channels activity through a differential mechanism. (15th October 2021)

• Record Type: Journal Article
• Authors: Staali, Leila; Colin, Didier A.
• Is Part Of: Toxicon. Volume 201(2021)
• Page Start: 74
• Page End: 85
• Publication Date: 2021-10-15
• Subjects: S. aureus -- Pore-forming toxins -- γ-hemolysins -- Neutrophils -- Ca2+ channels -- Protein kinase; PFTs pore-forming toxins -- PMN polymorphonuclear neutrophils -- PVL Panton-Valentin Leukocidins -- γ-hemolysins gamma-hemolysins -- H-89 N-[2-(p-bromocinnamylamino)ethyl]-5isoquinolinne-sulfonamide -- PKA protein kinase A -- PKC protein kinase C; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2021.08.007
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Staphylococcal bi-component leukotoxins known as *pore-forming toxins* induce upon a specific binding to membrane receptors, two independent cellular events in human neutrophils. First, they provoke the opening of pre-existing specific ionic channels including Ca 2+ channels. Then, they form membrane pores specific to monovalent cations leading to immune cells death. Among these leukotoxins, HlgC/HlgB and HlgA/HlgB γ-hemolysins do act in synergy to induce the opening of different types of Ca 2+ channels in the absence as in the presence of extracellular Ca 2+ . Here, we investigate the mechanism underlying the modulation of Ca 2+ -independent Ca 2+ channels in response to both active leukotoxins in human neutrophils. In the absence of extracellular Ca 2+, the Mn 2+ has been used as a Ca 2+ surrogate to determine the activity of Ca 2+ -independent Ca 2+ channels. Our findings provide new insights about different mechanisms involved in the staphylococcal γ-hemolysins activity to regulate three different types of Ca 2+ -independent Ca 2+ channels. We conclude that (i) HlgC/HlgB stimulates the opening of La 3+ -sensitive Ca 2+ channels, through a cholera toxin-sensitive G protein, (ii) HlgA/HlgB stimulates the opening of Ca 2+ channels not sensitive to La 3+, through a G protein-independent process, and (iii) unlike HlgA/HlgB, HlgC/HlgB toxins prevent the opening of a new type of Ca 2+ channels by phosphorylation/de-phosphorylation-dependent mechanisms. Highlights: Panton and Valentin Leucocidin (PVL) and γ-hemolysins from Staphylococcus aureus are bi-component leukotoxins. HlgC/HlgB and HlgA/HlgB γ-hemolysins do act in synergy to induce two independent cellular effects in human neutrophils. They induce the opening of Ca 2+ channels and form specific membrane pores leading to cells death. γ-hemolysins known as Ca 2+ channels agonists induce the opening of different types of ionic (Ca 2+, K +, Cl − ) channels. HlgC/HlgB and HlgA/HlgB do regulate the opening of Ca 2+ -independent Ca 2+ channels through a differential mechanism.