Aspartic Protease Inhibitors: Effective Drugs against the Human Fungal Pathogen Candida albicans

Abstract

Candida albicans can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis. C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape from the host immune responses. There is no doubt that the secretion of aspartic proteases, designated as Saps, is one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions. For these reasons, Saps clearly hold promise as new potential drug targets. Corroborating this hypothesis, the introduction of anti-human immunodeficiency virus drugs of the aspartic protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps. The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing the opportunistic infections, especially candidiasis. The attenuation of candidal infections in HIV-infected individuals might not solely has not only resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps as well as the blockage of several biological processes controlled by these proteolytic enzymes. The present article will discuss the updates on the functional implications of HIV PIs on the development of candidiasis. Keywords: Candida albicans, secreted aspartic proteases, aspartic protease inhibitors, alternative chemotherapy, candidiasis, virulence