An Ssd1 Homolog Impacts Trehalose and Chitin Biosynthesis and Contributes to Virulence inAspergillus fumigatus
ABSTRACTRegulation of fungal cell wall biosynthesis is critical to maintain cell wall integrity in dynamic fungal infection microenvironments. Genes involved in this response that impact fungal fitness and host immune responses remain to be fully defined. In this study, we observed that a yeastssd1homolog,ssdA, in the filamentous fungusAspergillus fumigatusis involved in trehalose and cell wall homeostasis. AnssdAnull mutant strain exhibited an increase in trehalose levels and a reduction in fungal colony growth rate. In contrast, overexpression ofssdAperturbed trehalose biosynthesis and reduced germination of conidia. ThessdAnull mutant strain was more resistant to cell wall-perturbing agents, while overexpression ofssdAincreased sensitivity. Overexpression ofssdAsignificantly increased chitin levels, and both loss and overexpression ofssdAaltered subcellular localization of the class V chitin synthase CsmA. Strikingly, overexpression ofssdAabolished adherence to abiotic surfaces and severely attenuated the virulence ofA. fumigatusin a murine model of invasive pulmonary aspergillosis. Despite the severein vitrofitness defects observed upon loss ofssdA, neither surface adherence nor murine survival was impacted. In conclusion,A. fumigatusSsdA plays a critical role in cell wall homeostasis impactingA. fumigatus-host interactions.IMPORTANCEThe incidence of life-threatening infections caused by the filamentous fungusAspergillus fumigatusis increasing along with an increase in the number of fungal strains resistant to contemporary antifungal therapies. The fungal cell wall and the associated carbohydrates required for its synthesis and maintenance are attractive drug targets given that many genes encoding proteins involved in cell wall biosynthesis and integrity are absent in humans. Importantly, genes and associated cell wall biosynthesis and homeostasis regulatory pathways remain to be fully defined inA. fumigatus. In this report, we identify SsdA as an important component of trehalose and fungal cell wall biosynthesis inA. fumigatusthat consequently impacts the host immune response and fungal virulence in animal models of infection.