title: 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.
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.
authors.affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Shallu
authors.initials: S
authors.lastname: Kathuria
authors.affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Cheshta
authors.initials: C
authors.lastname: Sharma
authors.affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Department of Pulmonary Medicine, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Department of Pulmonary Medicine, Rajan Babu Institute of Pulmonary Medicine and Tuberculosis, Delhi, India.
authors.forename: Kshitij
authors.initials: K
authors.lastname: Agarwal
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Ferry
authors.initials: F
authors.lastname: Hagen
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands; Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: Jacques F
authors.initials: JF
authors.lastname: Meis
authors.affiliation: Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Chowdhary
mesh_terms: D054458:Amplified Fragment Length Polymorphism Analysis; D001228:Aspergillosis / Q000382:microbiology; D001230:Aspergillus / Q000187:drug effects* / Q000302:isolation & purification; D025141:Drug Resistance, Fungal / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D005800:Genes, Fungal; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India; D008826:Microbial Sensitivity Tests; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D005656:Fungal Proteins