Master and Commander in Fungal Pathogens: the Two-Component System and the HOG Signaling Pathway

All living organisms, whether they be single- or multicellular, actively interact with their surrounding environments and modulate their physiological status to maintain cellular ho- meostasis. This adaptation process is highly coordinated via diverse signaling pathways, with the involvement of a series of signaling components, including sensors/receptors, kinases, and transcription factors. For microorganisms, the environ- ment is nonfavorable and can be considered a stress. Sensing and responding to a plethora of environmental stresses are key requirements for pathogenic fungi having a saprophytic life cycle, including Cryptococcus neoformans and Aspergillus fu- migatus, to colonize successfully and proliferate within the corresponding host system. In either commensal fungi that are able to cause opportunistic infection when the host immune system is compromised (e.g., Candida albicans) or parasitic fungi whose survival depends on the host without saprophytic cycles (e.g., Pneumocystis jirovecii, the dermatophytes, and the microsporidia), the stress-sensing and adaptation process is still required for survival at different host anatomical sites having distinct environmental conditions, during dissemination of organisms, or to counterbalance changes in overall host physiological conditions. These features confer an underlying distinction between pathogenic and nonpathogenic microbes, along with regulation of diverse virulence factors.