A unique group of scabies mite pseudoproteases promotes cutaneous blood coagulation and delays plasmin-induced fibrinolysis

• Published in: PLoS neglected tropical diseases 2021-01, Vol.15 (1), p.e0008997-e0008997
• Main Authors: Fernando, Deepani D, Reynolds, Simone L, Hartel, Gunter, Cribier, Bernard, Ortonne, Nicolas, Jones, Malcolm K, Fischer, Katja
• Format: Article
• Language: English
• Subjects: Animals; Biology and Life Sciences; Blood clot; Blood clotting; Blood Coagulation; Calcium - metabolism; Complications and side effects; Cysteine Proteases - analysis; Cysteine Proteases - physiology; Development and progression; Fibrin - biosynthesis; Fibrinolysin - pharmacology; Fibrinolysis; Health aspects; Humans; Medicine and Health Sciences; Mites; Physiological aspects; Proteases; Sarcoptes scabiei - enzymology; Scabies; Scabies - parasitology; Skin - blood supply; Thrombosis
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0008997

Scabies, a highly contagious skin disease affecting more than 200 million people worldwide at any time, is caused by the parasitic mite Sarcoptes scabiei. In the absence of molecular markers, diagnosis requires experience making surveillance and control challenging. Superficial microthrombi in the absence of vasculitis in scabies-affected skin are a recognised, yet unexplained histopathological differential of scabies infection. This study demonstrates that a family of Scabies Mite Inactivated Cysteine Protease Paralogues (SMIPP-Cs) excreted by the mites plays a role in formation of scabies-induced superficial microthrombi. A series of in vitro and ex vivo experiments involving two representative recombinant SMIPP-Cs was carried out. In the presence of SMIPP-Cs, the thrombin clotting time (TCT), fibrin formation and plasmin induced fibrinolysis were monitored in vitro. The ultrastructure of the SMIPP-C-modulated fibrin was analysed by Scanning Electron Microscopy (SEM). Immuno-histological analyses were performed ex vivo, to localise the SMIPP-C proteins within scabies infected skin biopsies. SMIPP-Cs displayed pro-coagulant properties. They bound calcium ions, reduced the thrombin clotting time, enhanced the fibrin formation rate and delayed plasmin-induced fibrinolysis. The SMIPP-Cs associated with fibrin clots during fibrinogen polymerisation and did not bind to preformed fibrin. Scanning electron microscopy revealed that the fibrin clots formed in the presence of SMIPP-Cs were aberrant and denser than normal fibrin clots. SMIPP-Cs were detected in microthrombi which are commonly seen in scabietic skin. The SMIPP-Cs are the first scabies mite proteins found in sub-epidermal skin layers and their pro-coagulant properties promote superficial microthrombi formation in scabetic skin. Further research is needed to evaluate their potential as diagnostic or therapeutic target.