In-vitro proteinase production by oral Candida albicans isolates from individuals with and without HIV infection and its attenuation by antimycotic agents

Abstract

In-vitro proteinase production by oral Candida afbicans isolates from patients with and without HIV infection (18 isolates from each group) was assessed by image analysis of a plate assay, with bovine serum albumin (BSA) as a substrate. The effect of subminimal inhibitory concentrations (sub-MICs) of nystatin, amphotericin B, clotrimazole and miconazole on in-vitro proteinase production by these yeast isolates was also investigated. Proteinase production by C. albicans isolates from patients with HIV infection was significantly greater than production by those from individuals without infection. All 18 isolates from HIV-infected individuals produced proteinase, in comparison to 56% of isolates from uninfected individuals. Pre-exposure of C. albicans isolates (seven proteinase producers from each group) to 1/4 and 1/16 MICs of nystatin, amphotericin B, clotrimazole and miconazole resulted in decreased proteinase production in all isolates tested. However, after exposure to the four antimycotic agents, proteinase production was decreased to a significantly greater extent in isolates from uninfected individuals than in those with HIV disease. Furthermore, when the relative concentration effect of antimycotic agents on proteinase production was compared, C. albicans isolates from the HIV-free group demonstrated a salient dose-response relationship compared with the HIV-infected group. These results indicate that C. albicans from patients with HIV infection are significantly more proteolytic than those from individuals without the infection, and that polyenes and imidazoles curtail the proteolytic activity of all C. afbicans isolates, albeit to a lesser extent in those from HIVinfected patients. It appears that HIV disease favours oral colonisation by more proteolytic C. afbicans isolates, with resilient proteolytic activity.

Increased expression of virulence attributes in oral Candida albicans isolates from human immunodeficiency virus-positive individuals

“…Similar to the results of Ollert et al (1995) and Wu et al (1996), we found increased expression of proteinase activity in isolates from HIV-infected individuals compared with HIV-uninfected subjects. The proteinases of C. albicans require a low pH for optimal activity.…”

“…The proteinases of C. albicans require a low pH for optimal activity. Interestingly, xerostomia, changes in salivary composition and the lower pH found in HIV-infected individuals favour the activity of proteinases (Wu et al, 1996).…”

Oral Candidal Infections and Antimycotics

“…Candida is also well-known to produce enzymes, such as secretory aspartyl proteinases (Saps), which facilitate both attachment to and penetration of the mucous membranes (Samaranayake and MacFarlane, 1990). Interestingly, subminimal inhibitory concentrations (sub-MIC) of amphotericin B are capable of curtailing the activity of this enzyme in oral C. albicans isolates (Wu et al, 1996), thus reducing its pathogenicity. On the contrary, exposure of C. albicans to sub-MIC of amphotericin B has resulted in enhanced resistance to apo-lactoferrin-mediated candidal cell death (Nikawa et al, 1994).…”

“…The proteolytic activity of oral C. albicans isolates in vitro is also curtailed by nystatin (Wu et al, 1996). However, similar to amphotericin B, exposure of C. albicans to sub-MIC of nystatin has resulted in an increased resistance to apo-lactoferrin-mediated cell death (Nikawa et al, 1994).…”

“…Further, subinhibitory concentrations of clotrimazole have been shown to curtail the proteinase production by oral C. albicans isolated from HIV-positive and HIV-negative individuals (Wu et al, 1996). In contrast, clotrimazole had no effect on the adherence of C. albicans to vaginal epithelial cells, in vitro, regardless of whether the drug was used to pre-treat the fungi or the vaginal epithelial cells or was added to the yeast/vaginal cell mixture (Odds and Webster, 1988).…”