Scabies: Molecular Perspectives and Therapeutic Implications in the Face of Emerging Drug Resistance

Kate E. Mounsey; Deborah C. Holt; James McCarthy; Bart J. Currie; Shelley F. Walton

Disclosures

Future Microbiol. 2008;3(1):57-66. 

In This Article

Scabies Mite Gene Discovery

Until recent years, there had been little progress in understanding the molecular biology of S. scabiei, primarily because of limitations in obtaining sufficient genetic material. Owing to their access to S. scabiei mites from crusted scabies patients, our group has overcome this problem, and initiated the first ever DNA-based studies on scabies in the mid-1990s.[58] We are now making rapid progress in our understanding of molecular mechanisms of both permethrin and ivermectin resistance in scabies mites. The partial genomic and cDNA sequence of the scabies mite voltage-sensitive sodium channel has been identified, facilitating single nucleotide polymorphism identification in permethrin-resistant mites.[59] Studies on permethrin resistant S. scabiei var. canis have identified a kdr type mutation not present in mites unexposed to permethrin, but this has not been identified in any var. hominis populations to date.[60] Two S. scabiei glutathione S-transferases have been identified and sequenced.[61,62] Eight ABC transporter genes have been recently identified from S. scabiei, five of which belong to subfamilies implicated in drug resistance in other organisms.[63] Subsequently, a quantitative PCR assay has been developed to study transcription of these genes and observed increased mRNA levels of an ABC transporter gene in ivermectin-exposed mites [Mounsey, Manuscript in prepraration]. Additionally, a novel ligand-gated chloride channel has been identified and characterized in the Xenopus laevis expression system. Significantly, this channel was irreversibly activated by ivermectin, suggesting it may act as a drug target in vivo.[64]

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