PubMed · 13370764
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L D ZEIDBERG. 1956. Soil studies.. https://pubmed.ncbi.nlm.nih.gov/13370764/
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Identifying fungal secreted factors that influence host infection remains a key challenge in microbial pathogenesis. While secreted effectors, particularly small cysteine-rich proteins, are well characterized in plant fungal pathogens, their counterparts in mammalian pathogens are understudied. We apply criteria from plant fungal effectors to the mammalian fungal pathogen Histoplasma, yielding a set of putative effectors highly enriched for knottins, proteins that adopt a distinctive cystine knot fold. Using an algorithm, we further identify 25 putative knottins in the Histoplasma genome, revealing a significant expansion of knottin genes. Knottin domains are found in diverse molecules but play an unknown role in virulence. Functional studies of individual Histoplasma knottins demonstrate their critical roles in intracellular survival and host cell lysis during macrophage infection as well as virulence in vivo. These findings highlight the importance of knottins in fungal pathogenesis and suggest their broader relevance for discovering conserved mechanisms of host manipulation.
Histoplasma capsulatum is a facultative intracellular pathogen, and the causative agent of the most common systemic fungal infection. Over the past several years, many new insights have been learned concerning the biology, biochemistry, and molecular genetics of this microorganism. This review focuses on the immunology of host defense against H. capsulatum yeasts with emphasis on the development of cell-mediated immunity, and the strategies used by the fungus to survive and multiply within macrophages.
Considerable information has accumulated recently about specific genes of Histoplasma capsulatum that are expressed during the process of adaptation when the organism undergoes morphological transition at the onset of infection. The study of these genes is crucial to identify targets for the development of novel antifungal agents.