Leukocidins: staphylococcal bi-component pore-forming toxins find their receptors

Abstract

PREFACE Staphylococcus aureus is a major bacterial pathogen that causes disease worldwide. The emergence of strains that are resistant to commonly used antibiotics and the failure of vaccine development has resulted in a renewed interest in the pathophysiology of S. aureus. The staphylococcal leukocidins are a family of bi-component pore-forming toxins that are important virulence factors. During the past five years, cellular receptors have been identified for all of the bi-component leukocidins. The identification of the leukocidin receptors explains the cellular tropism and species specificity that is exhibited by these toxins, which has important biological consequences. In this review, we summarize the recent discoveries that have refueled the interest in these toxins and we provide an outlook for future research.

Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

“…We verified the specificity and activity of the mutated and labeled toxins on the HEK-hC5aR cells. As expected, the toxins lysed only cells expressing hC5aR, whereas control hCCR2-expressing cells, which do not bind LukS (48), remained intact. We did not observe any binding of mF* on the same cells (Fig.…”

“…HEK cells transfected with hC5aR required higher toxin concentrations for optimal binding and lysis by mS + mF compared with PMN, which is in agreement with previous data for the wild-type variants. An explanation for this finding could be that PMNs also express another ligand for LukS, C5LR (or C5aR2), and LukF (48,49). It is known that C5aR expression levels are not stable in neutrophils but can easily change in natural settings, for example, as a response to increased C5a levels (50).…”

α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis

“…In addition to AT, other staphylococcal toxins such as the bi-component pore forming toxins; e.g. leukotoxin ED(Alonzo et al, 2013; Spaan et al, 2017), superantigens (Xu et al, 2014) and α-type phenol-soluble modulins (PSMs)(Wang et al, 2007) have all been attributed to play a role during bloodstream infections and facilitating organ damage, however none of these toxins appear to target platelets directly.…”

Vibrio cholerae cytolysin: Multiple facets of the membrane interaction mechanism of a β‐barrel pore‐forming toxin

“…The stoichiometry of the transmembrane pore complex depends on the specific types of the PFT under consideration. In most cases, homo‐oligomeric assembly of the PFT protomers generate the transmembrane pores , while in some cases, hetero‐oligomeric complexes involving more than one type of PFTs are also documented . In the mode of action of the PFTs, target membranes appear to act almost like a catalytic platform (although not possibly as a true catalyst) to trigger the structural/conformational reorganizations that are required for generating the transmembrane pore assembly.…”