Virulence-Associated Enzymes of Cryptococcus neoformans

Abstract

c Enzymes play key roles in fungal pathogenesis. Manipulation of enzyme expression or activity can significantly alter the infection process, and enzyme expression profiles can be a hallmark of disease. Hence, enzymes are worthy targets for better understanding pathogenesis and identifying new options for combatting fungal infections. Advances in genomics, proteomics, transcriptomics, and mass spectrometry have enabled the identification and characterization of new fungal enzymes. This review focuses on recent developments in the virulence-associated enzymes from Cryptococcus neoformans. The enzymatic suite of C. neoformans has evolved for environmental survival, but several of these enzymes play a dual role in colonizing the mammalian host. We also discuss new therapeutic and diagnostic strategies that could be based on the underlying enzymology.

A P4-ATPase subunit of the Cdc50 family plays a role in iron acquisition and virulence inCryptococcus neoformans

“…Disease in vertebrate hosts results from the ability of the fungus to grow at 37°C and to deliver key virulence traits to the cell surface. These factors include a polysaccharide capsule, the cell wall pigment melanin, and extracellular enzymes such as urease, phospholipase B, and acid phosphatase (Almeida, Wolf, & Casadevall, 2015;Djordjevic, 2010;Djordjevic, Del Poeta, Sorrell, Turner, & Wright, 2005;Doering, 2009;Idnurm et al, 2005;Kronstad et al, 2011;Zaragoza et al, 2009;Zhu & Williamson, 2004). The fungus must also resist killing by phagocytic cells and by oxidative and nitrosative mechanisms (Brown et al, 2007;Tucker & Casadevall, 2002).…”

Role of microglia in fungal infections of the central nervous system

“…65,66 Alternatively, the black pigment melanin may play a role in anti-phagocytic activity of C. neoformans. 67 In avirulent nonmelanogenic C. neoformans infected mice produced numerous key cytokines as described above without fatality, the virulent melanogenic fungi produces little or no cytokine secretion in mice with massive tissue damage and a number of fatalities. 68 The microglial response is critical against C. neoformans after CNS invasion.…”

Human fungal pathogens: Why should we learn?

“…C. neoformans is unique among human fungal pathogens as it is encapsulated by polysaccharides. Because the capsule and melanin formation, virulence-associated enzymes, and signaling pathways for pathogenicity have been recently reviewed elsewhere (O'Meara and Alspaugh, 2012;Bahn and Jung, 2013;Almeida et al, 2015;Choi et al, 2015), this special issue presents two reviews on the latest findings of host immune responses to C. neoformans and our current understanding of lipid modification and its role in C. neoformans virulence. The first review by Hole and Wormley (2016) focuses on innate host defenses against C. neoformans.…”