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Sulphur Metabolism of Fungi - Implications for Virulence and Opportunities for Therapy

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Fungal pathogens pose a serious threat to human health. Currently, it is estimated that they cause around 1.6 million deaths worldwide each year; however, the continuous increase of at risk populations and the emergence of antifungal resistance could translate into a grave increment of casualties due to ...

Fungal pathogens pose a serious threat to human health. Currently, it is estimated that they cause around 1.6 million deaths worldwide each year; however, the continuous increase of at risk populations and the emergence of antifungal resistance could translate into a grave increment of casualties due to fungal infections. The pathogenic potential of fungi, independently of whether they are acquired from the environment or are commensal in the human body, is strongly based on their extraordinary metabolic versatility, which permits them to adapt and thrive within a susceptible host’s tissues. Therefore, unravelling metabolism is a fundamental task in order to fully understand fungal virulence and to develop new strategies to fight them. Microbial metabolism serves the fundamental role of assimilating nutrients, anabolising them into building blocks of cellular physiology by biosynthetic routes, and catabolising macromolecules for metabolic turnover.

Among the various elements that biomolecules are composed of, sulphur is of special interest as it participates in many crucial, essential metabolic routes. Its exogenous assimilation and incorporation into biosynthetic pathways through the proteinogenic amino acids methionine and cysteine constitute the trans-sulphuration pathway, which is the core of sulphur metabolism. From there, sulphur derives and is incorporated in many different molecules that extend sulphur metabolism to a variety of processes relevant for cell homeostasis, fitness and also fungal virulence. For instance, redox homeostasis strongly relies on the sulphur-containing molecule glutathione, iron-sulphur clusters are essential co-factors of various enzymes, and some mycotoxins contain sulphur as active component.

Of particular relevance is the fact that several of the sulphur-dependent fungal processes are not well conserved in human cells, being either absent or differing significantly. Consequently, given its fundamental relevance for fungal viability and therefore pathogenicity, the study of sulphur metabolism opens opportunities for the identification of novel pan-fungal targets and the development of unprecedented antifungal therapies.


Keywords: Sulphur metabolism, Sulphur molecules, Fungal virulence, Target identification, Novel therapeutics


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