Characterization of a novel structural member, LukE‐LukD, of the bi‐component staphylococcal leucotoxins family

Abstract

A new member of the staphylococcal bi-component leucotoxins family, LukE (32 kDa) and LukD (34.3 kDa) has been characterized from Staphylococcus aureus strain Newman. LukE was 58^68% identical with the class S proteins, whereas LukD was 71^77% identical with the class F proteins of the family. A partial immunoreactivity with the various affinitypurified antibodies specific for the other proteins was observed. Immunoprecipitation assay and gene probing confirmed a 30% frequency among human clinical isolates, differing from the distribution of the other known leucotoxins (P 6 0.005). LukE+LukD was as effective as the Panton-Valentine leucocidin for inducing dermonecrosis when injected in the rabbit skin, but not hemolytic and poorly leucotoxic compared to other leucotoxins expressed by Staphylococcus aureus.z 1998 Federation of European Biochemical Societies.

Heavy chain-only antibodies and tetravalent bispecific antibody neutralizing Staphylococcus aureus leukotoxins

“…Human PMNs from healthy donors were purified from buffy coats as previously reported (13) and suspended at 5 × 10 5 cells/mL in 10 mM Hepes, 140 mM NaCl, 5 mM KCl, 10 mM glucose, 0.1 mM EGTA (pH 7.3).…”

“…One of the toxins, Panton-Valentine leukocidin (PVL) is associated with human pyogenic necrotizing skin infections such as furuncles, cellulitis, and abscesses, and more severe septic infections such as osteomyelitis, bacteremia, purpura fulminans, and necrotizing pneumonia (1)(2)(3)(4)(5)(6)(7)(8). PVL with γ-hemolysins (HlgA/HlgB and HlgC/ HlgB) and LukE/LukD belongs to the bicomponent pore-forming leukotoxin family (9)(10)(11)(12)(13)(14), which are thought to contribute to virulence in various infection models (15)(16)(17)(18), although some groups disagree (19,20). A class S and class F component interact sequentially and synergistically, inducing the activation and permeabilization of target cells and leading to their lysis.…”

Pathogenesis of microbial keratitis

“…Gamma-toxin, a two component toxin from S. aureus is composed of an F component and an S component that are non-toxic on their own. The S component binds to the target cell followed by binding of the F component both of which then move laterally in the cell membrane joining the other F-S pairs to form a ring that penetrates the membrane resulting in cell lysis [55,184]. The pathogenic role of gamma-and alpha-toxin were determined by Ref.…”

“…The strain deficient in either toxins were considerably less virulent compared to parent or rescued strains. S. aureus secretes several two component toxins each of which has its own S and F components [55]. This two component toxin system of S. aureus is complicated by the fact that S component of one toxin can also bind to the F component of the other toxin thereby creating several unique combinations with their own specific toxicity.…”

Staphylococcus aureusLukAB cytotoxin kills human neutrophils by targeting the CD11b subunit of the integrin Mac-1

“…Despite their common cellular target, the leukocidins diverge in their potency toward PMNs of different species. In particular, LukAB is extremely effective at killing human PMNs but not murine PMNs (12), a trait shared with PVL (16) but not LukED (14,(17)(18)(19). The basis of LukAB's tropism for human PMNs and other phagocytes has not been determined, but the recent identification of C-C chemokine receptor 5 (CCR5) as a cellular receptor used by LukED to kill lymphocytes, macrophages, and dendritic cells (14) suggests that other bicomponent leukocidins may use specific host factors to target and eliminate specific leukocytes.…”