Molecular characterization of Aspergillus terreus species complex clinical isolates: a multicentre study in eight university hospitals # EP390 S. Imbert1,2,3, A-C Normand4, S. Ranque4, JM. Costa5, C. Hennequin6, I. Accoceberry7, C. Bonnal1,8, S. Houzé8, A. Fekkar3, N. Bourgeois9, R. Piarroux4, E. Dannaoui2,10,11, F. Botterel1,2

Dynamyc 1 Unité de Parasitologie - Mycologie, Département de Microbiologie, DHU VIC, CHU Henri Mondor, AP-HP, Créteil, France; 2 EA Dynamyc 7380 UPEC, ENVA, Faculté de Médecine de Créteil, Créteil, France; 3 Service de Parasitologie-Mycologie, CHU La Pitié-Salpêtrière, AP-HP, Paris, France; 4 Service de Parasitologie-Mycologie, Hôpital de la Timone, Marseille, France; 5 Laboratoire CERBA, Saint Ouen L’Aumône, France; 6 Service de Parasitologie-Mycologie, AP-HP, Hôpital Saint Antoine, Paris, France; 7 Service de Parasitologie-Mycologie, CHU Bordeaux, France; 8 Service de Parasitologie-Mycologie, AP-HP, Hôpital Bichat, Paris, France; 9 Service de Parasitologie-Mycologie, CHU Montpellier, France; 10 Hôpital Européen Georges Pompidou APHP, Paris France; 11 Université Paris Descartes, Paris France.

Introduction Results

 Aspergillus terreus is one of the 5 most frequent  Eighty-two isolates were collected from 50 patients  Species identification pathogenic Aspergillus species after A. fumigatus. Aspergillus terreus sensu stricto A. terreus sensu stricto: n = 62 A. terreus Origin of isolates BCB01 btub  Infections due to can be problematic to manage A. citrinoterreus: n = 15 73 because of its intrinsic resistance to amphotericin B. HMN07 btub A. hortai: n =3 HEGP12 btub  A. terreus has been shown to be part of the A. terreus Paris (5 hospitals), 34 isolates PSL02 btub A. alabamensis: n = 2 species complex, currently comprising 14 recognized cryptic 92 LN680657 Aspergillus citrinoterreus species. All these species share morphological APHM06 btub APHM11 Btub characteristics and their prevalence in clinical samples is APHM23 btub Aspergillus citrinoterreus largely unknown. APHM24 Btub Bordeaux, 3 isolates 76 APHM26 btub Marseille, 44 isolates Aim of the study 87 APHM27 btub Montpellier, 1 isolate Neighbor-joining tree based on APHM36 Btub partial β-tubulin sequences HEGP05 btub  In this study we present the molecular characterization of HMN06 btub a panel of clinical isolates belonging to the A. terreus species  Mainly from respiratory samples (89%) 85 HMN09 btub complex and collected from 8 French university hospitals. HMN13 btub Underlying diseases HEGP06 btub PSL01 btub 76 95 Aspergillus hortai Methods 18 FJ491706 Aspergillus hortai 16 SAT02 Btub 14 84 EU147719 Aspergillus neoafricanus  Eighty-two clinical isolates were recovered from a variety 12 of specimens over a 13-year period (2003-2015). 10 EF669523 Aspergillus pseudoterreus 8 EU147769 Aspergillus alabamensis 6  For each isolate, age, sex, underlying disease of the 95 99 APHM03 btub Aspergillus alabamensis 4 89 APHM08 Btub patient, site of isolation and clinical form of aspergillosis 2 EF669524 Aspergillus auroterreus were retrieved. 0 Cystic fibrosis Chronic broncho- Haematological Solid organ Other condition FJ491714 Aspergillus floccosus  Isolates were initially identified as members of A. terreus pulmonary disease malignancy transplant EF669532 Aspergillus neoindicus EF669528 Aspergillus niveus species complex by morphological characteristics. 99  Clinical forms EF669531 Aspergillus allahabadii 74  Each isolate was identified to the species level by Mainly bronchial colonization: n = 44 EF669529 Aspergillus carneus sequencing a part of the β-tubulin and calmodulin genes. EF669534 Aspergillus ambiguus Invasive aspergillosis: n = 5 (A. terreus sensu stricto) 98 EF669515 Aspergillus microcystus  Neighbor-joining trees were built to perform phylogenetic HEGP2885 A flavus Onychomycosis: n = 1 (A. hortai) analyses (MEGA 6.0 software). PSL03 A fumigatus

0.05 References Conclusion 1. Guinea J, 2015. J Clin Microbiol 53(2): 611-7 For the first time in France, we molecularly characterized a large collection of clinical isolates belonging to A. terreus species complex. 2. Hachem R, 2014. J Antimicrob Chemother 69: 3148-55 A. terreus sensu stricto was the most common species and was responsible for the 5 cases of invasive aspergillosis. However, 25% of these clinical isolates were cryptic species other than A. terreus sensu stricto. Further studies are warranted to investigate the clinical Contact : [email protected], [email protected] impact of these cryptic species, as well as their antifungal susceptibility.