Elevated aspartic proteinase secretion and experimental pathogenicity of Candida albicans isolates from oral cavities of subjects infected with human immunodeficiency virus

Abstract

Isolates of Candida albicans from the oral cavities of subjects at different stages of human immunodeficiency virus (HIV) infection or uninfected controls were examined for (i) production of aspartic proteinase(s), a putative virulence-associated factor(s); (ii) the presence in the fungal genome of two major genes (SAP1 and SAP2) of the aspartic proteinase family; and (iii) experimental pathogenicity in a murine model of systemic infection. It was found that the fungal isolates from symptomatic patients secreted, on average, up to eightfold more proteinase than the isolates from uninfected or HIV-infected but asymptomatic subjects. This differential property was stably expressed by the strains even after years of maintenance in stock cultures. Moreover, representative high-proteinase isolates were significantly more pathogenic for mice than low-proteinase isolates of C. albicans. The characters high proteinase and increased virulence were not associated with a single molecular type or category identifiable through DNA fingerprinting or pulsed-field electrophoretic karyotype, and both SAP1 and SAP2 genes were present in both categories of isolates, on the same respective chromosomes. In conclusion, our data suggest that during HIV infection more-virulent strains or biotypes of C. albicans which are identifiable by direct analysis of virulence determinants are selected. It also appears that the biotype switch to increased aspartic proteinase and virulence properties occurs before the HIV-infected subject enters the symptomatic stage and overt AIDS.

HIV-1 and its transmembrane protein gp41 bind to differentCandidaspecies modulating adhesion

“…We have then corroborated our hypothesis that this direct interaction may in part be responsible for the altered virulence of C. albicans in HIV-positive subjects [12] by demonstrating an augmentation of fungal virulence properties in vitro following HIV binding [16]. In particular, phagocytosis by polymorphonuclear leukocytes was decreased [16], whereas secretion of aspartic proteinases (Saps), one of the major virulence factors of C. albicans [17,18], produced to a higher extent by C. albicans isolates from HIV-positive individuals compared to isolates from uninfected subjects [19,20], was found to be increased after this interaction [16]. An involvement of Saps in gp41 binding itself, e.g.…”

Frequency and enzymatic activity of Candida albicans isolated from the oral cavity of HIV-positive patients at Fortaleza, Ceará

“…Other studies carried out in Brazil showed that this activity was present in about 53% to 100% of Candida albicans cultures (13,14,19) . According to international data, proteinase activity was detected in 16% to 100% of the studied samples (2,3,6,8,12) . Our study did not find a correlation between in vitro proteolytic activity and the severity of the lesion.…”

Oral candidiasis in HIV+ patients under treatment with protease inhibitors

“…Virulence factors from C. albicans were shown to be more expressive in HIV-carrier individuals. 20,21 The frequency of oral candidiasis in HIV+ patients varies among the different reports, and can af-fect up to 94% of infected individuals. However, the prevalence of candidiasis in HIV+ individuals has diminished.…”