Abstract
BackgroundScabies 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 FindingsBlood 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/SignificanceWe 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.
Highlights
Scabies is a ubiquitous and contagious skin infection caused by a burrowing parasitic mite Sarcoptes scabiei
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
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
Summary
Scabies is a ubiquitous and contagious skin infection caused by a burrowing parasitic mite Sarcoptes scabiei. Staphylococcus aureus and Streptococcus pyogenes are the common causative agents of scabies associated pyoderma [7,8]. Methicillin resistant S. aureus (MRSA) has been reported in 64% of children presented with scabies in a regional hospital of North West Queensland [10]. Given that scabies is a primary risk factor for bacterial skin infections and increased incidence of MRSA infections, it is of increasing relevance to understand the molecular links in the trilateral relationship of host, mites and bacteria. 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. We show that a recently characterized mite serine protease inhibitor (SMSB4) inhibits the complement-mediated blood killing of S. aureus
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