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

被引:48
作者
Kathuria, Shallu [1 ]
Sharma, Cheshta [1 ]
Singh, Pradeep Kumar [1 ]
Agarwal, Puneet [2 ]
Agarwal, Kshitij [3 ]
Hagen, Ferry [4 ]
Meis, Jacques F. [4 ,5 ]
Chowdhary, Anuradha [1 ]
机构
[1] Univ Delhi, Vallabhbhai Patel Chest Inst, Dept Med Mycol, Delhi 110007, India
[2] Univ Delhi, Vallabhbhai Patel Chest Inst, Dept Pulm Med, Delhi 110007, India
[3] Rajan Babu Inst Pulm Med & TB, Dept Pulm Med, Delhi, India
[4] Canisius Wilhelmina Hosp, Dept Med Microbiol & Infect Dis, Nijmegen, Netherlands
[5] Radboudumc, Dept Med Microbiol, Nijmegen, Netherlands
来源
PLOS ONE | 2015年 / 10卷 / 03期
关键词
EMERGING FUNGAL PATHOGEN; AMPHOTERICIN-B; MIC DISTRIBUTIONS; CUTOFF VALUES; FUMIGATUS; INFECTIONS; SPP; VORICONAZOLE; RESISTANCE; PATIENT;
D O I
10.1371/journal.pone.0118997
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Aspergillus terreus is emerging as an etiologic agent of invasive aspergillosis in immuno-compromised 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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页数:17
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