Dr Jacqueline Upcroft

Position: Senior Research Fellow (SRF)
Major area of interest: Molecular Parasitology

My research focuses are understanding drug susceptibility and resistance, pathogenicity, virulence, host range and host/parasite interactions at the molecular, genetic and cellular levels for Giardia duodenalis, Trichomonas vaginalis and Entamoeba histolytica. These three organisms are anaerobic protozoan pathogens infecting over one billion people world-wide each year. Giardia causes severe diarrhoea, failure-to-thrive syndrome; Trichomonas causes vaginitis, acute inflammatory disease, preterm delivery, low birth-weight, predisposition to HIV infection and cervical cancer; and Entamoeba is responsible for dysentery and potentially fatal abscesses.

Drug resistance with Peter Upcroft (QIMR), Rakesh Sehgal (India), Nitaya Thammapalerd (Thailand), Roberto Cedillo (Mexico), Zygmunt Kazimierczuk (Poland) and Patrice Vanelle (France)

My laboratory cloned the first Giardia gene encoding a protein (pyruvate:ferredoxin oxidoreductase, PFOR) directly involved in resistance to the most commonly used antigiardial drug, metronidazole. Since then my laboratory has identified the major pathways involved in drug resistance against all commonly available drugs used to treat giardiasis. We have studied the mechanism of resistance in each case and discovered that the four different drug classes available induce different pathways of resistance in the parasite. Ongoing work involves elucidating a multi-drug resistance pathway and redesigning and screening new drugs (designed by our colleagues in France and Poland) to overcome existing drug resistance pathways.

Entamoeba histolytica and Trichomonas vaginalis are metabolically similar to Giardia and it has been appropriate, therefore, to investigate the mechanism of metronidazole resistance in these organisms, especially, since metronidazole is the only drug available to treat amoebiasis and trichomoniasis. We instigated the induction of the first reported metronidazole resistance in E. histolytica and we have shown that, unlike the situation in Giardia and Trichomonas, PFOR is not involved in metronidazole resistance. Instead superoxide dismutase (SOD) which targets toxic radicals produced by the activated drugs is increased in drug-resistant lines. Ongoing and future work is focussing on the different mechanisms of resistance seen between clinically resistant and laboratory induced drug-resistant lines of Trichomonas. With our colleague in India we are persuing the monitoring of metronidazole resistance of E. histolytica.

Drug susceptibility assays with Peter Upcroft (QIMR), Linda Dunn (QIMR), Wim Sturm (South Africa), John Reeder (PNG), Frank Sorvillo (USA) and Suzanne Garland (Melbourne)

I have developed a rapid, simplified drug susceptibility assay which has been suggested as the reference assay from drug resistance monitoring of Giardia, Trichomonas and Entmaoeba. I will continue to use this assay to monitor drug susceptibility, treatment failures and reinfections in clinical isolates, in collaboration with colleagues, from South Africa, India, Thailand, Mexico, Europe and from local sources.