A Scabies Mite Serpin Interferes with Complement-Mediated Neutrophil Functions and Promotes Staphylococcal Growth

Background Scabies is a contagious skin disease caused by the parasitic mite Sarcoptes scabiei. The disease is highly prevalent worldwide and known to predispose to secondary bacterial infections, in particular by Streptococcus pyogenes and Staphylococcus aureus. Reports of scabies patients co-infected with methicillin resistant S. aureus (MRSA) pose a major concern for serious down-stream complications. We previously reported that a range of complement inhibitors secreted by the mites promoted the growth of S. pyogenes. Here, we show that a recently characterized mite serine protease inhibitor (SMSB4) inhibits the complement-mediated blood killing of S. aureus. Methodology/Principal Findings Blood killing of S. aureus was measured in whole blood bactericidal assays, counting viable bacteria recovered after treatment in fresh blood containing active complement and phagocytes, treated with recombinant SMSB4. SMSB4 inhibited the blood killing of various strains of S. aureus including methicillin-resistant and methicillin-sensitive isolates. Staphylococcal growth was promoted in a dose-dependent manner. We investigated the effect of SMSB4 on the complement-mediated neutrophil functions, namely phagocytosis, opsonization and anaphylatoxin release, by flow cytometry and in enzyme linked immuno sorbent assays (ELISA). SMSB4 reduced phagocytosis of S. aureus by neutrophils. It inhibited the deposition of C3b, C4b and properdin on the bacteria surface, but did not affect the depositions of C1q and MBL. SMSB4 also inhibited C5 cleavage as indicated by a reduced C5b-9 deposition. Conclusions/Significance We postulate that SMSB4 interferes with the activation of all three complement pathways by reducing the amount of C3 convertase formed. We conclude that SMSB4 interferes with the complement-dependent killing function of neutrophils, thereby reducing opsonization, phagocytosis and further recruitment of neutrophils to the site of infection. As a consequence secreted scabies mites complement inhibitors, such as SMSB4, provide favorable conditions for the onset of S. aureus co-infection in the scabies-infected microenvironment by suppressing the immediate host immune response.
Author Summary There is increasing evidence that in the tropics bacterial pyoderma and life-threatening downstream complications caused by Staphylococcus aureus and Streptococcus pyogenes are often linked with scabies infestation. The bacteria were commonly thought to find easy entry into the skin, damaged by scabies mites. However, there may be more to it. Our study aimed to identify the molecular mechanisms underlying the link between mites and bacteria. We recently characterized a molecule (SMSB4) that the mite produces for self-protection from the immediate host defense system in the skin. We show here that SMSB4 reduces the uptake of S. aureus by neutrophils, which are the killer immune cells, first to arrive at the infection site. These cells are guided by a number of complement factors. SMSB4 reduces the deposition of several complement components on the bacteria surface, thereby interrupting the essential defense cascades and inhibiting further neutrophil recruitment to the site. In summary, a mite molecule that likely originally evolved to protect the mite against the host defense plays a further role in the pathogenesis of secondary infections: when secreted into the damaged skin it promotes the onset of S. aureus infection thereby increasing the prevalence of debilitating disease associated with scabies.