Detection of azole resistance in Aspergillus fumigatus complex isolates using MALDI-TOF mass spectrometry
| Autor: | Margarita Estreya Zvezdanova, Manuel J. Arroyo, Gema Méndez, Ana Candela, Luis Mancera, Julio García Rodríguez, Julia Lozano Serra, Rosa Jiménez, Inmaculada Lozano, Carmen Castro, Concepción López, Patricia Muñoz, Jesús Guinea, Pilar Escribano, Belén Rodríguez-Sánchez, Waldo Sánchez-Yebra, Juan Sánchez-Gómez, Eduardo Marfil, Montserrat Muñoz de la Rosa, Rocío Tejero García, Fernando Cobo, Antonio Rezusta, Teresa Peláez, Cristian Castelló-Abietar, Isabel Costales, Cristina Labayru Echeverría, Cristina Losa Pérez, Gregoria Megías-Lobón, Belén Lorenzo, Ferrán Sánchez-Reus, Josefina Ayats, María Teresa Martín, Inmaculada Vidal, Victoria Sánchez-Hellín, Elisa Ibáñez, Javier Pemán, Miguel Fajardo, Carmen Pazos, María Rodríguez-Mayo, Ana Pérez-Ayala, Elia Gómez, Julia Serrano, Elena Reigadas, Belén Rodríguez, Estreya Zvezdanova, Judith Díaz-García, Ana Gómez-Núñez, José González Leiva, Marina Machado, Isabel Sánchez-Romero, Julio García-Rodríguez, José Luis del Pozo, Manuel Rubio Vallejo, Carlos Ruiz de Alegría-Puig, Leyre López-Soria, José María Marimón, Diego Vicente, Marina Fernández-Torres, Silvia Hernáez-Crespo |
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| Rok vydání: | 2022 |
| Předmět: |
Azoles
0301 basic medicine Microbiology (medical) Species complex Antifungal Agents Sequence analysis 030106 microbiology ASPERGILLUS FUMIGATUS COMPLEX Azole resistance Microbial Sensitivity Tests Gene mutation Biology Mass spectrometry Aspergillus fumigatus 03 medical and health sciences 0302 clinical medicine Drug Resistance Fungal parasitic diseases Humans 030212 general & internal medicine Genetics chemistry.chemical_classification General Medicine bacterial infections and mycoses biology.organism_classification Infectious Diseases chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Azole |
| Zdroj: | Clinical Microbiology and Infection. 28:260-266 |
| ISSN: | 1198-743X |
| DOI: | 10.1016/j.cmi.2021.06.005 |
| Popis: | Objectives The main goal of this study was to accurately detect azole resistance in species of the Aspergillus fumigatus complex by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Methods Identification of isolates (n = 868) was done with MALDI-TOF MS using both commercial and in-house libraries. To determine azole susceptibility, the EUCAST E.Def. 9.3.2 method was applied as the reference standard. Identification of resistant isolates was confirmed by DNA sequence analysis. Protein spectra obtained by MALDI-TOF MS were analysed to differentiate species within the A. fumigatus complex and to detect azole-resistant A. fumigatus sensu stricto isolates. Results Correct discrimination of A. fumigatus sensu stricto from cryptic species was accomplished in 100% of the cases applying principal component analysis (PCA) to protein spectra generated by MALDI-TOF MS. Furthermore, a specific peak (4586 m/z) was found to be present only in cryptic species. The application of partial least squares (PLS) discriminant analysis allowed 98.43% (±0.038) discrimination between susceptible and azole-resistant A. fumigatus sensu stricto isolates. Finally, based on PLS and SVM, A. fumigatus sensu stricto isolates with different cyp51A gene mutations were correctly clustered in 91.5% of the cases. Conclusions MALDI-TOF MS combined with peak analysis is a novel tool that allows the differentiation of A. fumigatus sensu stricto from other species within the A. fumigatus complex, as well as the detection of azole-resistant A. fumigatus sensu stricto. Although further studies are still needed, the results reported here show the great potential of MALDI-TOF and machine learning for the rapid detection of azole-resistant Aspergillus fumigatus isolates from clinical origins. |
| Databáze: | OpenAIRE |
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