Abstract
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.
Highlights
Invasive aspergillosis (IA) is a devastating and difficult to manage disease, which is associated with significantly high morbidity and mortality, especially in immunocompromised patients with haematological malignancy or recipients of allogeneic hematopoietic stem cell transplantation [1,2,3]
We aimed to study the population structure of a large collection of 140 molecularly characterized A. terreus isolates from various hospitals and the environment in Delhi, India and its adjoining regions, using a robust microsatellite based typing technique and Amplified Fragment Length Polymorphism (AFLP) analysis
The present study characterized a large number of A. terreus isolates using short tandem repeats (STR) typing
Summary
Invasive aspergillosis (IA) is a devastating and difficult to manage disease, which is associated with significantly high morbidity and mortality, especially in immunocompromised patients with haematological malignancy or recipients of allogeneic hematopoietic stem cell transplantation [1,2,3]. Samson et al (2011) [14], using a polyphasic approach, described seven lineages among A. terreus isolates. They proposed 7 species in Aspergillus section Terrei namely A. terreus sensu stricto, A. alabamensis, A. floccosus, A. neoafricanus, A. aureoterreus, A. hortai and A. pseudoterreus [14]. Only two studies, originating from the USA had explored the population structure of global A. terreus isolates [18, 19]. The data obtained by genotyping methods revealed the presence of a recently delineated cryptic species, A. hortai in the Aspergillus section Terrei, as an etiologic agent of aspergilloma and IA, not reported previously
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