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Aspergillus terreus  is emerging as an etiologic agent of invasive aspergillosis in immunocompromised individuals in several medical centers in the world. Infections due to  A .  terreus  are of concern due to its resistance to amphotericin B,  in vivo  and  in vitro , resulting in poor response to antifungal therapy and high mortality. Herein we examined a large collection of molecularly characterized, geographically diverse  A .  terreus  isolates (n = 140) from clinical and environmental sources in India for the occurrence of cryptic  A .  terreus  species. The population structure of the Indian  A .  terreus  isolates and their association with those outside India was determined using microsatellite based typing (STR) technique and Amplified Fragment Length Polymorphism analysis (AFLP). Additionally,  in vitro  antifungal susceptibility of  A .  terreus  isolates was determined against 7 antifungals. Sequence analyses of the calmodulin locus identified the recently described cryptic species  A .  hortai , comprising 1.4% of  Aspergillus  section  Terrei  isolates cultured from cases of aspergilloma and probable invasive aspergillosis not reported previously. All the nine markers used for STR typing of  A .  terreus  species complex proved to be highly polymorphic. The presence of high genetic diversity revealing 75 distinct genotypes among 101 Indian  A .  terreus  isolates was similar to the marked heterogeneity noticed in the 47 global  A .  terreus  population exhibiting 38 unique genotypes mainly among isolates from North America and Europe. Also, AFLP analysis showed distinct banding patterns for genotypically diverse  A .  terreus  isolates. Furthermore, no correlation between a particular genotype and amphotericin B susceptibility was observed. Overall, 8% of the  A .  terreus  isolates exhibited low MICs of amphotericin B. All the echinocandins and azoles (voriconazole, posaconazole and isavuconazole) demonstrated high potency against all the isolates. The study emphasizes the need of molecular characterization of  A .  terreus  species complex isolates to better understand the ecology, acquisition and transmission of this species.

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Molecular Epidemiology and In-Vitro Antifungal Susceptibility of Aspergillus terreus Species Complex Isolates in Delhi, India: Evidence of Genetic Diversity by Amplified Fragment Length Polymorphism and Microsatellite Typing