Stress Signaling Pathways for the Pathogenicity of Cryptococcus

Abstract

Sensing, responding, and adapting to the surrounding environment are crucial for all living organisms to survive, proliferate, and differentiate in their biological niches. This ability is also essential for Cryptococcus neoformans and its sibling species Cryptococcus gattii, as these pathogens have saprobic and parasitic life cycles in natural and animal host environments. The ability of Cryptococcus to cause fatal meningoencephalitis is highly related to its capability to remodel and optimize its metabolic and physiological status according to external cues. These cues act through multiple stress signaling pathways through a panoply of signaling components, including receptors/sensors, small GTPases, secondary messengers, kinases, transcription factors, and other miscellaneous adaptors or regulators. In this minireview, we summarize and highlight the importance of several stress signaling pathways that influence the pathogenicity of Cryptococcus and discuss future challenges in these areas.

Cryptococcus neoformans and Cryptococcus gattii, the Etiologic Agents of Cryptococcosis

“…neoformans produces many degradation enzymes; some of them have been confirmed as virulence determinants. Urease (Cox et al 2000Osterholzer et al 2009;Shi et al 2010;Bahn and Jung 2013;Singh et al 2013) and phospholipase B Ganendren et al 2006;Wright et al 2007;Chayakulkeeree et al 2011) are the two most studied degradation enzymes that have a role in cryptococcal pathogenicity. The functions of these enzymes promote intracellular survival of the yeasts (Wright et al 2007), hydrolysis of host cell membranes to penetrate into tissue (Chen et al 1997), immunomodulation (Noverr et al 2003;Osterholzer et al 2009), and the enhancement of fungal dissemination from the lung to the brain (Cox et al 2000;Noverr et al 2003;Wright et al 2007;Shi et al 2010;Singh et al 2013).…”

Cryptococcus gattii Infections

“…Additional genes, transcription factors, and signaling molecules that have been linked to virulence in C. gattii are summarized in Table 3. A recent comprehensive review of stress signaling pathways and the pathogenicity of Cryptococcus was provided by Bahn and Jung (139). Other virulencerelated functions in C. neoformans are likely to be conserved in C. gattii.…”

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.…”