Pore formation by a two-component leukocidin from Staphyloccocus aureus within the membrane of human polymorphonuclear leukocytes

Antibody-mediated enhancement of community-acquired methicillin-resistant Staphylococcus aureus infection

“…Among the family of related S. aureus two-component toxins, PVL has the most potent activity in terms of activating proinflammatory mediators from granulocytes (12,28,29). Above a certain threshold, PVL multimerizes to form pores in membranes of PMNs, resulting in PMN lysis (11), which might contribute to virulence when bacterial levels increase in the presence of insufficient neutralizing antibody.…”

“…PVL is a bicomponent pore-forming toxin composed of the LukF and LukS proteins encoded by the corresponding genes present in tandem on a bacteriophage lysogenized within the S. aureus chromosome (10). Previous work with these types of toxins has shown that they can lyse polymorphonuclear neutrophils (PMNs) and monocytes of the white blood cell lineage (11,12); however, importantly, at sublytic levels, staphylococcal leukocidins also have a strong proinflammatory effect on granulocytes (12). Whereas dissimilar outcomes from different investigators analyzing the contribution of PVL to virulence in experimental settings can be attributed to the use of different S. aureus strains and different infection systems for analysis of virulence, as well as different mouse strains, key factors related to human infections have not been incorporated into these previous evaluations.…”

Enhancement of bacterial virulence by antibody neutralization of immune-activating toxins

“…3 PVL is made up of multimers of two protein subunits, LukS and LukF, which assemble into a pore-like complex that lyses polymorphonuclear (PMN) and monocytic cell lineages of certain mammals, including those of humans. 4,5 Based on this known function of PVL, it seems simple to assume that it would be a virulence factor for S. aureus by disabling a key host factor needed to control infection. However, studies in the past several years have yielded contradictory findings as to whether PVL is a virulence factor for CA-MRSA, [6][7][8][9] putting into question the role that PVL plays in staphylococcal infections despite, or in addition to, its pore forming capabilities.…”

Characterisation of a synergohymenotropic toxin produced by Staphylococcus intermedius

“…The target cells of these toxins are host defence cells such as neutrophils, monocytes and macrophages, and also erythrocytes according to the proteins [20]. This family of toxins was termed synergohymenotropic (SHT) toxins because of the synergistical aspect of class S and class F components which may be intergangeable [20] and because they are membrane damaging toxins [6,10].…”

“…The biological activity results in the formation of pores of divalent ion size [10], thus activating neutrophils at sub-lytic levels which are responsible for neosynthesis and secretion of inflammatory mediators such as leukotrien B4, interleukine-8, and histamine [14,17,23]. Inflammatory lesions can be observed after the intradermal injection of toxins to rabbits where PVL is responsible for acute necrosis [9,32].…”