Abstract
Nutrient uptake is essential for cellular life and the capacity to perceive extracellular nutrients is critical for coordinating their uptake and metabolism. Commensal fungal pathogens, e.g., Candida albicans, have evolved in close association with human hosts and are well-adapted to using diverse nutrients found in discrete host niches. Human cells that cannot synthesize all amino acids require the uptake of the “essential amino acids” to remain viable. Consistently, high levels of amino acids circulate in the blood. Host proteins are rich sources of amino acids but their use depends on proteases to cleave them into smaller peptides and free amino acids. C. albicans responds to extracellular amino acids by pleiotropically enhancing their uptake and derive energy from their catabolism to power opportunistic virulent growth. Studies using Saccharomyces cerevisiae have established paradigms to understand metabolic processes in C. albicans; however, fundamental differences exist. The advent of CRISPR/Cas9-based methods facilitate genetic analysis in C. albicans, and state-of-the-art molecular biological techniques are being applied to directly examine growth requirements in vivo and in situ in infected hosts. The combination of divergent approaches can illuminate the biological roles of individual cellular components. Here we discuss recent findings regarding nutrient sensing with a focus on amino acid uptake and metabolism, processes that underlie the virulence of C. albicans.
Highlights
All organisms require nutrients to live, grow and successfully reproduce
S. cerevisiae paved the way for most of our understanding of nutrient assimilation and metabolic processes in yeasts, there are clearly significant differences that exist in C. albicans that must be taken into account as they are crucial to our understanding of how this fungal pathogen assimilate nutrients in the host, especially in the context of infectious growth
Some of the so-called poor or non-preferred nitrogen sources in S. cerevisiae, such as proline, are efficiently utilized by C. albicans. This observation is in alignment with recent findings that the enzymes required to utilize proline in C. albicans are independent of Nitrogen catabolite repression (NCR), allowing the unrestricted utilization of proline regardless of whether other nitrogen sources are available [59,60]
Summary
All organisms require nutrients to live, grow and successfully reproduce. The ability of an organism to assimilate nutrients in a given ecological niche is dependent on its ability to sense and respond to the availability of nutrients and on intrinsic cellular properties. C. albicans is a natural commensal of humans, capable of colonizing virtually all anatomical sites (Figure 1) This fungus can switch from harmless commensal to pathogenic growth and thereby cause a spectrum of pathologies, ranging from mucosal to life-threatening systemic infections, collectively termed candidiasis. C. albicans in the blood can enter urine via the kidney, resulting in candiduria the bloodstream again, allowing them to the reach additional anatomical sites, and in rare cases (yeast the (cerebral). We begin by introducing some basic concepts regarding nitrogen source utilization and assimilation and present a more focused discussion regarding amino acid metabolism, the generation of ammonia and associated consequences, and the central role of mitochondria in the production of energy for virulent growth
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