isolates from New York outbreak are highly pathogenic with measurable experimental disease in .

causes prolonged colonization and bloodstream infections in hospitalized patients. Different clades vary in their geographic origin, disease spectrum, and antifungal resistance, but biological basis underlying such variations needs further examination. Therefore, we investigated susceptible and multidrug-resistant isolates, obtained early in the New York outbreak, to benchmark their pathogenic potential in caterpillar worms of greater wax moth . Healthy worms responded to in a strain-specific, dose-responsive pattern. Three drug-resistant, clade I 17-1, 18-1, and 18-2 isolates caused high mortality, while a control, drug-susceptible, clade II 16-1 caused lower mortality ( < 0.001) with graded inocula (1 × 10 to 1 × 10 CFU). Virulence correlated with fungal growth in hemolymph as 17-1, 18-1 and 18-2 reached high fungal cell load in the infected larvae, while 16-1 multiplied less proficiently. The degree of melanization was higher in worms infected with more pathogenic . Hemocoel histopathology showed more fungal elements and about 50 granulomas per profile for 17-1, 18-1 and 18-2 compared to 5 to 10 granulomas for 16-1. With more pathogenic isolates, the expression of gallerimycin, ceropin, and galiomycin increased significantly ( < 0.05). Thus, the induction of immune effector peptides, histopathological responses, and melanization are proportionate to pathogenic potential. However, from different vendors showed unpredictable quality upon delivery that impacted feasibility and reproducibility of planned studies. Our results indicate utility of experimental model for screening of pathogenesis depending upon quality of worms commercially available in the USA.IMPORTANCEThe New York metropolitan area continues to suffer from the largest, ongoing outbreak of drug-resistant . It is necessary to gather more information to determine if isolates from this outbreak vary in their ability to cause more severe disease in affected patients. Therefore, we studied the experimental model of greater wax moth . We found that susceptible and drug-resistant NY isolates caused measurable disease in . There was a good correlation between pathogenic potential of and melanin in the infected worms, fungal elements in worm hemolymph, uptick in the genes involved in insect immunity, and histopathological changes. The worms sourced from various commercial vendors were of variable quality. We confirm that remains a facile model to study experimental disease.