Abstract
Methicillin resistant Staphylococcus aureus (MRSA) is a major human pathogen, which causes superficial to lethal clinical infections. Neutrophils are the most abundant leukocytes in the blood and are the first defense mechanism against S. aureus infections. Here we show Staphylococcal Superantigen-Like protein 11 (SSL11) from MRSA USA300_FPR3757 mediated differentiated human neutrophil-like cells (dHL60) motility arrest by inducing cell adhesion and “locking” cells in adhesion stage, without inducing oxidative burst. Pre-incubation of SSL11 with the glycan Sialyl Lewis X blocked SSL11 function and de-glycosylation of dHL60 cells by PNGase F abolished SSL11 binding, suggesting that SSL11 functions via interacting with glycans. This is the first description of a bacterial toxin inhibiting neutrophil motility by inducing adhesion and “locking” cells in an adhesion stage. Therefore, this study might provide a new target against S. aureus infections.
Highlights
Staphylococcus aureus (S. aureus) is a major opportunistic pathogen of humans, which causes superficial complications to lethal, invasive infections
Staphylococcal Superantigen-Like protein 11 (SSL11) showed a dramatic decrease in expression when S. aureus was co-cultured with L. reuteri RC-14 and recombinant SSL11 reacted with all five convalescent human sera samples from patients with previous S. aureus infections[12], suggesting that SSL11 plays an important role for S. aureus infections
A quantitative plate assay showed that SSL11 induced Differentiated HL60 cells (dHL60) cell adhesion in a dose-dependent manner, with 40 nM SSL11 inducing about 50% cell adhesion (Fig. 1C)
Summary
Staphylococcus aureus (S. aureus) is a major opportunistic pathogen of humans, which causes superficial complications to lethal, invasive infections. S. aureus survival in humans requires evasion of the host immune system, where complement activation and neutrophil-mediated killing are the primary defense mechanisms[2]. Understanding immune modulating protein SSL11 from MRSA might provide new targets against S. aureus infections. Neutrophils are the most abundant leukocytes and the first host immune defense against S. aureus infection. The evasion of host neutrophil recruitment to the site of infection is essential to the success of S. aureus as a pathogen[2]. We show for the first time that SSL11 disrupts neutrophil motility by induction of cell adhesion. These findings provide a new therapeutic target against S. aureus infections and neutrophil overstimulated inflammatory diseases
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