Azole resistance in Aspergillus fumigatus isolates from respiratory specimens in Lyon University Hospitals, France: prevalence and mechanisms involved

Autor: Damien Dupont, Bruno Lina, A. Sénéchal, Meja Rabodonirina, Isabelle Durieu, Sébastien Couraud, Tanguy Déméautis, Florence Persat, Gilles Devouassoux, Loïc Simon, Martine Wallon, Eric Dannaoui, Philippe Reix, Rolf Kramer, Jean Menotti, Héloïse Garnier
Přispěvatelé: Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon] (CNR - laboratoire associé), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), European Public Health Microbiology Training Programme (EUPHEM), European Centre for Disease Control, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), hôpital Louis-Pradel, CHU de Lyon, 69500 Bron, France., Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Cité (UPCité), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de parasitologie et mycologie médicale [Hôpital de la Croix Rousse, Lyon]
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Antimicrobial Agents
International Journal of Antimicrobial Agents, 2021, 58 (6), pp.106447. ⟨10.1016/j.ijantimicag.2021.106447⟩
ISSN: 1872-7913
0924-8579
Popis: Resistance of Aspergillus fumigatus to triazoles has been reported increasingly in Europe. As few data are available from Southern France, the objectives of this study were to assess the burden of A. fumigatus isolates with azole resistance from clinical specimens in Lyon, and explore the resistance mechanisms involved. In this retrospective cross-sectional study, 221 consecutive A. fumigatus isolates from respiratory samples were identified from an 8-month period from 195 patients attending the Pulmonary Medicine Departments of Lyon University Hospitals. Morphological identification was confirmed by sequence analysis of the β-tubulin gene. All samples were tested for susceptibilities to itraconazole, voriconazole, posaconazole and isavuconazole using concentration gradient strips, and the results were confirmed using the EUCAST broth microdilution method. Resistance mechanisms were investigated by sequencing the cyp51A gene and its promoter, and by expression analysis of cyp51 and genes encoding several efflux transporters. Four isolates exhibited azole resistance. Three isolates presented with polymorphisms in an intronic region of cyp51A, and one isolate had F46Y, M172V and E427K polymorphisms. No mutations were identified in the cyp51A promoter, but significant induction of cyp51A and cyp51B gene expression was observed for all four and three isolates, respectively. Significant induction of atrF and cdr1B gene expression was observed for two and three isolates, respectively. No significant induction of MDR1/2/3/4, MFS56 and M85 gene expression was observed. To conclude, the observed prevalence of azole resistance was 2.1%. Significant induction of expression of the cyp51 genes and two genes encoding efflux transporters was evidenced, underlying the diversity of resistance mechanisms to be explored.
Databáze: OpenAIRE
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