Scabies mite complement inhibitors as targets for novel therapeutics
In Australia, Aboriginal and Torres Strait Islander people are affected by scabies, associated rheumatic heart, renal disease and staphylococcal infections at a much greater rate than the non-Indigenous population. Available therapies are limited. Our project is at the forefront of a new agenda to define the underlying links between mites, bacteria and patient. We have discovered scabies mite molecules that interfere with a critical part of the immediate immune defence (the human complement system). As such they are likely essential to the parasites and consequently, potential drug targets. Further, they promote the growth of S.pyogenes and S.aureus in human plasma, which determines them as a key factor in the development of life-threatening bacterial co-infections.
Substantial groundwork for this project was produced by PhD candidate Simone Reynolds (CIB), who was funded through a QIMR program. She is the first Indigenous PhD candidate to graduate at QIMR and worked in a small laboratory dedicated, since 2000, to research this neglected disease affecting Aboriginal and Torres Strait Islander Australians. Simone has been part of the QIMR team since 2006.
The project aimed to understand the biology of the parasite and its interplay with bacterial pathogens through:
- Defining the complement binding sites in scabies mite inactivated protease paralogues serine (SMIPP-Ss).
- Investigating the biological role of scabies mite inactivated protease paralogues cysteine (SMIPP-Cs).
- Investigating the role of mite complement inhibitors in scabies-associated S.aureus infections in vitro.
Findings included identification of mite proteins involved in a synergetic interaction between mites and bacteria. These proteins seemed to act as inhibitors to metabolic pathways that normally would attack the mite and prevent the infection.
Related resources:
- Swe, P. & Fischer, K. 2014, A Scabies Mite Serpin Interferes with Complement-Mediated Neutrophil Functions and Promotes Staphylococcal Growth, PLOS Neglected Tropical Diseases, vol 8, no 6, DOI: 10.1371/journal.pntd.0002928.
- Reynolds, L., Pike, R., Mika A., Blom, A., Hofmann, A., Wijeyewickrema, L., Kempand, D. & Fischer, K., 2014, Scabies Mite Inactive Serine Proteases Are Potent Inhibitors of the Human Complement Lectin Pathway, PLOS Neglected Tropical Diseases, vol 8, no 5, DOI: 10.1371/journal.pntd.0002872.
