Staphylococcus aureus Leukotoxin GH Promotes Inflammation

Staphylococcus aureus is a prominent cause of bacterial infections worldwide. The pathogen produces a variety of molecules that presumably facilitate survival in or on the human host (reviewed in [1]). Bicomponent, pore-forming leukotoxins are among the secreted molecules produced by S. aureus. These molecules have cytolytic activity toward leukocytes, most notably polymorphonuclear leukocytes (PMNs) and mononuclear phagocytes. Some of these leukotoxins, such as Panton-Valentine leukocidin (PVL), are encoded on mobile genetic elements such as prophage, whereas others are encoded by genes located in the core genome and are thus present in the majority of strains [2–4]. Bicomponent leukotoxins are composed of S and F subunits that oligomerize and assemble into a β-barrel pore in the plasma membrane of host cells [2, 5]. Recently we and others described a new member of the leukotoxin family—LukGH (named LukAB by DuMont et al [6])—that is an abundant surface-associated and freely secreted protein of S. aureus [3]. Although these studies demonstrated that LukGH causes lysis of phagocytes in vitro and promotes S. aureus colonization and survival in the mouse, our understanding of the role of this molecule during S. aureus infection remains incomplete [3, 6]. To address this deficiency in knowledge, we tested the ability of purified LukGH to elicit an inflammatory response in the skin of mammals (monkey, rabbit, and mouse) and evaluated contribution of the toxin to the severity of S. aureus infection in mice and rabbits.