Scabies Laboratory

David Kemp Staff
Funding
Collaborators
Recent Publications
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Lab Head: Professor David Kemp

Scabies mite

Molecular biology of scabies mites
Katja Fischer, Simone Reynolds,Masego Johnstone and David Kemp

Scabies is a disease of worldwide importance caused by burrowing of the parasitic mite Sarcoptes scabiei into the lower stratum corneum of the epidermis. Infestation with Sarcoptes scabiei causes an allergic type skin reaction with visible hypersensitivity lesions and pruritus and results in significant morbidity primarily due to secondary infections with pathogenic bacteria. Until very recently there were no molecular studies on scabies because of the difficulty of obtaining mites. We have solved this problem by constructing a library of expressed Sarcoptes scabiei sequences from mites obtained from skin shed into the bedding of patients with the severe form of the disease, crusted scabies.

Sarcoptes Over 40,000 of these clones have been sequenced in collaboration with Deborah Holt, MSHR, Darwin and the Australian Genome Research Facilty, providing a major resource for future studies. In search for drug targets and vacine candidates we have chosen to focus our research on gut molecules and searched the cDNA database for homologues of the major allergens of house dust mites, the group 1 cysteine proteases and group 3 serine proteases. Unexpectedly, we identified multigene families of both S. scabiei group 1 and group 3 homologues. The remarkable feature of these is that they encode both active proteases as well as molecules which have the amino acids essential for catalysis mutated and thus cannot function as active proteases by any known mechanism. These had no counterparts in a library of house dust mite sequences.

Based on this data, we hypthesize that the genes for inactivated proteases have been amplified in the scabies mite genome to mediate novel host defence evasion strategies. We propose that they have evolved as an adaptation to parasitism of the epidermis and may present unanticipated approaches to protective intervention. In collaboration with Ashley Buckle, James Whisstock and Rob Pike at Monash University, Melbourne high resolution structures for two Inactivated Serine Protease Paralogues (SMIIPP-Ss) has been determined and binding properties studied.

Complement is one host defence system that has evolved to limit the capacity of pathogenic parasites to survive and multiply within the epidermis. We have discovered that SMIPP-Ss inhibit complement presumably protecting the mite from complement-mediated gut damage. This is an essential requirement for the mite as its gut fills with epidermal and serum proteins during feeding. The mechanism of this is currently under study in collaboration with Ashley Buckle at Monash University, Melbourne and Anna Blom's Research Group at Lund University in Malmö, Sweden.

ANIMATION: Skin crust with scabies mites
Movie courtesy of Charlene Willis (former PhD student in the Scabies Laboratory 2007)

Staff

Labhead: Professor Dave Kemp

Research Officer: Dr Katja Fischer
Angela Mika

Research Assistant: Simone Reynolds

Postdoctoral Fellow: Dr Masego Johnstone

Katja Fishcher Simone Reynolds Masego Johnstone Angela Mika

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Funding

The National Health and Medical Research Council

Collaborators

Recent Publications

Willis C, Fischer K, Walton S, Currie BJ and Kemp DJ. Scabies Mite Inactivated Serine Protease Paralogues are present both internally in the mite gut and externally in faeces. Am. J. Trop. Med. Hyg 75: 683-687, 2006

Pasay C, Walton S, Fischer K, Holt D, McCarthy J (2006) PCR-based assay to survey for knockdown resistance to pyrethroid acaricides in human scabies mites (Sarcoptes scabiei var hominis) Am J Trop Med Hyg 74: 649-657, 2006

O'Neil SE, Heinrich TK, Hales BJ, Hazell LA, Holt DC, Fischer K and Thomas, WR. The chitinase allergens Der p 15 and Der p 18 from Dermatophagoides pteronyssinus. Clinical and Experimental Allergy, 36, 831-839, 2006.

Dougall A, Holt DC, Fischer K, Currie BJ, Kemp DJ, Walton SF. Identification and Characterization of Sarcoptes scabiei and Dermatophagoides pteronyssinus glutathione Stransferases: implication as a potential major allergen in crusted scabies. Parasitol Res 34: 839-49, 2005

Mounsey KE, Holt DC, Fischer K, Kemp DJ, Currie BJ and Walton SF. Analysis of Sarcoptes scabiei finds no evidence of infection with Wolbachia. Int. J. Parasitol 131-135, 2005

Fischer K, Holt DC, Currie BJ, Walton SF, Kemp DJ, (2006) Scabies mite inactivated protease paralogues. In Streptococci - New Insights into an old enemy. International Congress Series 1289. Elsevier, Amsterdam, The Netherlands. pp85-88.

Arlian LG, Morgan MS, Estes SA, Walton SF, Kemp DJ., Currie BJ. Circulating IgE in patients with ordinary and crusted scabies. J. Med. Entomol 41: 74-77, 2004

Holt DC, Fischer K, Currie BJ, Walton SF, Kemp DJ. A multigene family of inactivated cysteine proteases in Sarcoptes scabiei. J. Invest. Dermatol 123: 240-241, 2004

McCarthy JS, Kemp DJ, Walton SF and Currie BJ. Scabies: more than just an irritation. Postgraduate Medical Journal 80: 382-387, 2004

Walton SF, Holt DC, Currie BJ and Kemp DJ. Scabies: New future for a neglected disease. Advances in Parasitol 57: 309-376, 2004

Walton SF, Dougall A, Pizzutto S, Holt DC, Taplin D, Arlian LG, Morgan M, Currie BJ, Kemp DJ. Genetic epidemiology of Sarcoptes scabiei (Acari: Sarcoptidae) in northern Australia. Int. J. Parasitol 34:(7) 839-849, 2004

Holt DC, Fischer K, Allen GE, Wilson D, Wilson P, Slade R, Currie, BJ Walton, SF and Kemp DJ. Mechanisms for a novel immune evasion strategy in the scabies mite Sarcoptes scabiei ; a multigene family of inactivated serine proteases. J. Invest. Dermatol 121: 1419-1424, 2003

Holt DC, Fischer K, Allen GE, Wilson D, Wilson P, Slade R, Currie BJ, Walton SF and Kemp DJ. Mechanisms for a novel immune evasion strategy in the scabies mite. Sarcoptes scabiei:a multigene family of inactivated serine proteases. J. Invest. Dermatol. 121, 2003

Good MF, Sriprakash KS and Kemp DJ. Vaccine control strategies against Group A streptococcal infections; expectations, hopes and possible impact. Infectiology, 2003

Harumal P, Morgan M, Walton SF, Holt DC, Rode J, Arlian LG, Currie BJ, and Kemp DJ. Identification of a homologue of a house dust mite allergen in a cDNA library from Sarcoptes scabiei var. hominis and evaluation of its vaccine potential in a rabbit/ S. scabiei var. canis model. Am. J. Trop. Med. Hyg. 68: 54-60, 2003

Fischer K, Holt DC, Harumal P, Currie BJ, Walton SF and Kemp DJ. Generation and Characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library; Identification of homologues of house dust mite allergens. Am. J. Trop. Med. Hyg. 68: 61-64, 2003

Skerrat LF, Campbell N, Walton SW, Kemp DJ and Barker SC. The mitochondrial 12S gene is a suitable marker of populations of Sarcoptes scabiei from wombats, dogs and humans in Australia. Parasitology Research 88(4): 376-9, 2003

Fischer K, Holt DC, Wilson P, Davis J, Hewitt V, Johnson M, McGrath, V. Currie BJ, Walton SF and Kemp DJ. Normalization of a library of Sarcoptes scabiei cDNAs cloned in lZAP by a long PCR and cDNA reassociation procedure. Biotechniques 34: 250-254, 2003

Harumal P, Holt DC, Fischer K, Walton S and Kemp DJ. A spectrum of gene sequence analysis in Australia: Towards a vaccine for Scabies. Today's Life Science (Genomics in Australia Special Issue) 13(5): 34, 2001.

Labhead:	Professor Dave Kemp
Research Officer:	Dr Katja Fischer Angela Mika
Research Assistant:	Simone Reynolds
Postdoctoral Fellow:	Dr Masego Johnstone