1 |
The effects of anti-HIV nucleoside drugs on the virulence of clinically relevant candida speciesAhmadou, Ahidjo Bintou 26 February 2007 (has links)
Student Number: 0420652W -
MSc(Med) Dissertation -
School of Pathology -
Faculty of Health Sciences / Candida species are opportunistic yeasts that cause infections in immunocompromised
individuals such as HIV and cancer patients. Recent studies show that 5fluorouracil,
a
nucleoside analogue used for cancer treatment, increases Candida cell virulence. The aim
of this study is to determine the effects of commonly used antiHIV
nucleoside analogue
drugs on the virulence of Candida albicans, the predominant species associated with oral
candidiasis.
Oral swabs were collected from antiretroviralnaïve
HIVpositive
individuals. C. albicans
was characterised from 39 of these swabs using standard microbiological techniques and
polymerase chain reaction. The effect of nucleoside reverse transcriptase inhibitors
(NRTIs) zidovudine, stavudine, didanosine and lamivudine, at predicted drug peak
concentrations in patients, as well as half and double these concentrations on select
virulence factors of C. albicans isolates were studied. In addition, antifungal
susceptibility to amphotericin B was assessed. Not all 39 isolates were used in the assays
because of delays in obtaining reagents from respective manufacturers.
Results show no change in the adherence and biofilm formation of 29 isolates upon
exposure to NRTIs. In contrast, a steady increase in the number of viable cells was
observed upon exposure to double the peak concentration of lamivudine to 23 of the
clinical isolates. All 31 isolates tested were susceptible to amphotericin B (MIC£1mg/ml).
Although these results suggest that NRTIs may have little effect on the virulence of C.
albicans it is postulated, that, in a dosedependent
manner, cytidine analogues act
similarly to 5FU
by activating a signaltransduction
pathway which stimulates
proliferation.
|
Page generated in 0.0818 seconds