Abstract
Over the past 20 years, emerging antifungal resistance has been observed in the human pathogen, Aspergillus fumigatus, and is responsible for serious infections. Resistance in this pathogenic fungus is mainly due to the unintended impact of triazole fungicides widely used in the environment to protect crops and materials from destroying fungi. A. fumigatus is naturally present in the environment and will thus be widely exposed to fungicides, which, through selection pressure, will favour strains that have become resistant. These fungicidal compounds have a chemical structure similar to that of medical compounds, thus rendering them inactive for the treatment of an infection in humans with a resistant strain. A. fumigatus does not cause infections in crops yet fungicidal compounds with activity against this widely present fungus select for an unintended cross-resistance. Therefore, it is important to understand the phenomena leading to resistance in the environment.
In this chapter, we first reviewed resistance mechanisms that have been described, both occurring under medical treatments and those rather attributed to environmental fungicidal use. We have detailed its spread from its probable origin in Europe to its current global distribution. Then, a focus on environmental contributing factors leading to resistance was done and in particular the cross-disciplinary use of azoles. We defined what can be considered as a hotspot of resistance selection and discussed the possible abiotic and biotics factors in soils implicated in the resistance emergence. Finally, we have considered various possibilities to stop the increase of this phenomenon: limit the uncontrolled spread of fungicides in the environment on the one hand and to reduce the exposure of fungicides on the other hand.
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References
Abdolrasouli A, Rhodes J, Beale MA, Hagen F, Rogers TR, Chowdhary A, Meis JF, Armstrong-James D, Fisher MC (2015) Genomic context of azole resistance mutations in Aspergillus fumigatus determined using whole-genome sequencing. MBio 6:e00536–e00536. https://doi.org/10.1128/mBio.00536-15
Ahangarkani F, Puts Y, Nabili M, Khodavaisy S, Moazeni M, Salehi Z, Laal Kargar M, Badali H, Meis JF (2020) First azole-resistant Aspergillus fumigatus isolates with the environmental TR46/Y121F/T289A mutation in Iran. Mycoses 63:430–436. https://doi.org/10.1111/myc.13064
Ahmad S, Khan Z, Hagen F, Meis JF (2014) Occurrence of triazole-resistant Aspergillus fumigatus with TR34/L98H mutations in outdoor and hospital environment in Kuwait. Environ Res 133:20–26. https://doi.org/10.1016/j.envres.2014.05.009
Ahmad S, Joseph L, Hagen F, Meis JF, Khan Z (2015) Concomitant occurrence of itraconazole-resistant and -susceptible strains of Aspergillus fumigatus in routine cultures. J Antimicrob Chemother 70:412–415. https://doi.org/10.1093/jac/dku410
Albarrag AM, Anderson MJ, Howard SJ, Robson GD, Warn PA, Sanglard D, Denning DW (2011) Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter. Antimicrob Agents Chemother 55:5113–5121. https://doi.org/10.1128/AAC.00517-11
Alvarez-Moreno C, Lavergne RA, Hagen F, Morio F, Meis JF, Le Pape P (2017) Azole-resistant Aspergillus fumigatus harboring TR34/L98H, TR46/Y121F/T289A and TR53 mutations related to flower fields in Colombia. Sci Rep 7:45631. https://doi.org/10.1038/srep45631
Alvarez-Moreno C, Lavergne RA, Hagen F, Morio F, Meis JF, Le Pape P (2019) Fungicide-driven alterations in azole-resistant Aspergillus fumigatus are related to vegetable crops in Colombia, South America. Mycologia 111:217–224. https://doi.org/10.1080/00275514.2018.1557796
Amorim A, Guedes-Vaz L, Araujo R (2010) Susceptibility to five antifungals of Aspergillus fumigatus strains isolated from chronically colonised cystic fibrosis patients receiving azole therapy. Int J Antimicrob Agents 35:396–399. https://doi.org/10.1016/j.ijantimicag.2009.12.007
Ashu EE, Hagen F, Chowdhary A, Meis JF, Xu J (2017) Global population genetic analysis of Aspergillus fumigatus. mSphere 2:e00019-17. https://doi.org/10.1128/mSphere.00019-17
Astvad KM, Jensen RH, Hassan TM, Mathiasen EG, Thomsen GM, Pedersen UG, Christensen M, Hilberg O, Arendrup MC (2014) First detection of TR46/Y121F/T289A and TR34/L98H alterations in Aspergillus fumigatus isolates from azole-naive patients in Denmark despite negative findings in the environment. Antimicrob Agents Chemother 58:5096–5101. https://doi.org/10.1128/AAC.02855-14
Azevedo MM, Faria-Ramos I, Cruz LC, Pina-Vaz C, Rodrigues AG (2015) Genesis of azole antifungal resistance from agriculture to clinical settings. J Agric Food Chem 63:7463–7468. https://doi.org/10.1021/acs.jafc.5b02728
Badali H, Vaezi A, Haghani I, Yazdanparast SA, Hedayati MT, Mousavi B, Ansari S, Hagen F, Meis JF, Chowdhary A (2013) Environmental study of azole-resistant Aspergillus fumigatus with TR34/L98H mutations in the cyp51A gene in Iran. Mycoses 56:659–663. https://doi.org/10.1111/myc.12089
Bader O, Weig M, Reichard U, Lugert R, Kuhns M, Christner M, Held J, Peter S, Schumacher U, Buchheidt D, Tintelnot K, Gross U (2013) cyp51A-based mechanisms of Aspergillus fumigatus azole drug resistance present in clinical samples from Germany. Antimicrob Agents Chemother 57:3513–3517. https://doi.org/10.1128/AAC.00167-13
Bader O, Tunnermann J, Dudakova A, Tangwattanachuleeporn M, Weig M, Gross U (2015) Environmental isolates of azole-resistant Aspergillus fumigatus in Germany. Antimicrob Agents Chemother 59:4356–4359. https://doi.org/10.1128/AAC.00100-15
Balmas V, Delogu G, Sposito S, Rau D, Migheli Q (2006) Use of a complexation of tebuconazole with beta-cyclodextrin for controlling foot and crown rot of durum wheat incited by Fusarium culmorum. J Agric Food Chem 54:480–484. https://doi.org/10.1021/jf0523014
Bellete B, Raberin H, Morel J, Flori P, Hafid J, Manhsung RT (2010) Acquired resistance to voriconazole and itraconazole in a patient with pulmonary aspergilloma. Med Mycol 48:197–200. https://doi.org/10.3109/13693780902717018
Berger S, El Chazli Y, Babu AF, Coste AT (2017) Azole resistance in Aspergillus fumigatus: a consequence of antifungal use in agriculture? Front Microbiol 8:1024. https://doi.org/10.3389/fmicb.2017.01024
Berkow EL, Nunnally NS, Bandea A, Kuykendall R, Beer K, Lockhart SR (2018) Detection of TR34/L98H CYP51A mutation through passive surveillance for azole-resistant Aspergillus fumigatus in the United States from 2015 to 2017. Antimicrob Agents Chemother 62:e02240-17. https://doi.org/10.1128/AAC.02240-17
Bradley K, Drijber RA, Knops J (2006) Increased N availability in grassland soils modifies their microbial communities and decreases the abundance of arbuscular mycorrhizal fungi. Soil Biol Biochem 38:1583–1595. https://doi.org/10.1016/j.soilbio.2005.11.011
Bromley MJ, van Muijlwijk G, Fraczek MG, Robson G, Verweij PE, Denning DW, Bowyer P (2014) Occurrence of azole-resistant species of Aspergillus in the UK environment. J Glob Antimicrob Res 2:276–279. https://doi.org/10.1016/j.jgar.2014.05.004
Buil JB, Hare RK, Zwaan BJ, Arendrup MC, Melchers WJG, Verweij PE (2019) The fading boundaries between patient and environmental routes of triazole resistance selection in Aspergillus fumigatus. PLoS Pathog 15:e1007858. https://doi.org/10.1371/journal.ppat.1007858
Burgel PR, Baixench MT, Amsellem M, Audureau E, Chapron J, Kanaan R, Honore I, Dupouy-Camet J, Dusser D, Klaassen CH, Meis JF, Hubert D, Paugam A (2012) High prevalence of azole-resistant Aspergillus fumigatus in adults with cystic fibrosis exposed to itraconazole. Antimicrob Agents Chemother 56:869–874. https://doi.org/10.1128/AAC.05077-11
Bustamante B, Illescas LR, Posadas A, Campos PE (2020) Azole resistance among clinical isolates of Aspergillus fumigatus in Lima-Peru. Med Mycol 58:54–60. https://doi.org/10.1093/mmy/myz032
Čadková E, Komárek M, Kaliszová R, Vaněk A, Balíková M (2013) Tebuconazole sorption in contrasting soil types. Soil Sediment Contam 22:404–414. https://doi.org/10.1080/15320383.2013.733448
Camps SM, van der Linden JW, Li Y, Kuijper EJ, van Dissel JT, Verweij PE, Melchers WJ (2012) Rapid induction of multiple resistance mechanisms in Aspergillus fumigatus during azole therapy: a case study and review of the literature. Antimicrob Agents Chemother 56:10–16. https://doi.org/10.1128/AAC.05088-11
Chen J, Li H, Li R, Bu D, Wan Z (2005) Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J Antimicrob Chemother 55:31–37. https://doi.org/10.1093/jac/dkh507
Chen Y, Lu Z, Zhao J, Zou Z, Gong Y, Qu F, Bao Z, Qiu G, Song M, Zhang Q, Liu L, Hu M, Han X, Tian S, Chen F, Zhang C, Sun Y, Verweij PE, Huang L, Han L (2016) Epidemiology and molecular characterizations of azole resistance in clinical and environmental Aspergillus fumigatus isolates from China. Antimicrob Agents Chemother 60:5878–5884. https://doi.org/10.1128/AAC.01005-16
Chen Y, Dong F, Zhao J, Fan H, Qin C, Li R, Verweij PE, Zheng Y, Han L (2020) High azole resistance in Aspergillus fumigatus isolates from strawberry fields, China, 2018. Emerg Infect Dis 26:81–89. https://doi.org/10.3201/eid2601.190885
Chowdhary A, Kathuria S, Randhawa HS, Gaur SN, Klaassen CH, Meis JF (2012a) Isolation of multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR/L98H mutations in the cyp51A gene in India. J Antimicrob Chemother 67:362–366. https://doi.org/10.1093/jac/dkr443
Chowdhary A, Kathuria S, Xu J, Sharma C, Sundar G, Singh PK, Gaur SN, Hagen F, Klaassen CH, Meis JF (2012b) Clonal expansion and emergence of environmental multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR34/L98H mutations in the cyp51A gene in India. PLoS One 7:e52871. https://doi.org/10.1371/journal.pone.0052871
Chowdhary A, Kathuria S, Xu J, Meis JF (2013) Emergence of azole-resistant Aspergillus fumigatus strains due to agricultural azole use creates an increasing threat to human health. PLoS Pathog 9:e1003633. https://doi.org/10.1371/journal.ppat.1003633
Chowdhary A, Sharma C, Kathuria S, Hagen F, Meis JF (2014a) Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A mutation in India. J Antimicrob Chemother 69:555–557. https://doi.org/10.1093/jac/dkt397
Chowdhary A, Sharma C, van den Boom M, Yntema JB, Hagen F, Verweij PE, Meis JF (2014b) Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania. J Antimicrob Chemother 69:2979–2983. https://doi.org/10.1093/jac/dku259
Chowdhary A, Sharma C, Kathuria S, Hagen F, Meis JF (2015) Prevalence and mechanism of triazole resistance in Aspergillus fumigatus in a referral chest hospital in Delhi, India and an update of the situation in Asia. Front Microbiol 6:428. https://doi.org/10.3389/fmicb.2015.00428
Crini G, Fourmentin S, Fenyvesi É, Torri G, Fourmentin M, Morin-Crini N (2018) Cyclodextrins, from molecules to applications. Environ Chem Lett 16:1361–1375. https://doi.org/10.1007/s10311-018-0763-2
Dauchy C, Bautin N, Nseir S, Reboux G, Wintjens R, Le Rouzic O, Sendid B, Viscogliosi E, Le Pape P, Arendrup MC, Gosset P, Fry S, Frealle E (2018) Emergence of Aspergillus fumigatus azole resistance in azole-naive patients with chronic obstructive pulmonary disease and their homes. Indoor Air 28:298–306. https://doi.org/10.1111/ina.12436
de Ramón-Carbonell M, Sánchez-Torres P (2020) Significance of 195 bp-enhancer of PdCYP51B in the acquisition of Penicillium digitatum DMI resistance and increase of fungal virulence. Pestic Biochem Physiol 165:104522. https://doi.org/10.1016/j.pestbp.2020.01.003
Del Valle EMM (2004) Cyclodextrins and their uses: a review. Process Biochem 39:1033–1046. https://doi.org/10.1016/S0032-9592(03)00258-9
Diaz-Guerra TM, Mellado E, Cuenca-Estrella M, Rodriguez-Tudela JL (2003) A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 47:1120–1124. https://doi.org/10.1128/aac.47.3.1120-1124.2003
Dousset S, Thevenot M, Schrack D, Gouy V, Carluer N (2010) Effect of grass cover on water and pesticide transport through undisturbed soil columns, comparison with field study (Morcille watershed, Beaujolais). Environ Pollut 158:2446–2453. https://doi.org/10.1016/j.envpol.2010.03.028
Dunne K, Hagen F, Pomeroy N, Meis JF, Rogers TR (2017) Intercountry transfer of triazole-resistant Aspergillus fumigatus on plant bulbs. Clin Infect Dis 65:147–149. https://doi.org/10.1093/cid/cix257
El Azhari N, Dermou E, Barnard RL, Storck V, Tourna M, Beguet J, Karas PA, Lucini L, Rouard N, Botteri L, Ferrari F, Trevisan M, Karpouzas DG, Martin-Laurent F (2018) The dissipation and microbial ecotoxicity of tebuconazole and its transformation products in soil under standard laboratory and simulated winter conditions. Sci Total Environ 637–638:892–906. https://doi.org/10.1016/j.scitotenv.2018.05.088
Fischer J, van Koningsbruggen-Rietschel S, Rietschel E, Vehreschild MJ, Wisplinghoff H, Kronke M, Hamprecht A (2014) Prevalence and molecular characterization of azole resistance in Aspergillus spp. isolates from German cystic fibrosis patients. J Antimicrob Chemother 69:1533–1536. https://doi.org/10.1093/jac/dku009
Fisher MC, Hawkins NJ, Sanglard D, Gurr SJ (2018) Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science 360:739–742. https://doi.org/10.1126/science.aap7999
Garcia-Rubio R, Cuenca-Estrella M, Mellado E (2017) Triazole resistance in Aspergillus species: an emerging problem. Drugs 77:599–613. https://doi.org/10.1007/s40265-017-0714-4
Gisi U (2014) Assessment of selection and resistance risk for demethylation inhibitor fungicides in Aspergillus fumigatus in agriculture and medicine: a critical review. Pest Manag Sci 70:352–364. https://doi.org/10.1002/ps.3664
GLASS (2016) 2nd Meeting of the global antimicrobial resistance surveillance system collaborative platform with global report available online: https://www.who.int/antimicrobial-resistance/events/2nd-GLASS-collaborative-platform-meeting/en/
Godeau C, Reboux G, Scherer E, Laboissiere A, Lechenault-Bergerot C, Millon L, Rocchi S (2019) Azole-resistant Aspergillus fumigatus in the hospital: surveillance from flower beds to corridors. Am J Infect Control 48:702–704. https://doi.org/10.1016/j.ajic.2019.10.003
Gonzalez-Lara MF, Roman-Montes CM, Diaz-Lomeli P, Rangel-Cordero A, Valenzuela MO, Ponce-de-Leon A, Sifuentes-Osornio J, Ostrosky-Zeichner L, Martinez-Gamboa A (2019) Azole resistance and cyp51A mutation screening in Aspergillus fumigatus in Mexico. J Antimicrob Chemother 74:2047–2050. https://doi.org/10.1093/jac/dkz121
Gsaller F, Hortschansky P, Furukawa T, Carr PD, Rash B, Capilla J, Muller C, Bracher F, Bowyer P, Haas H, Brakhage AA, Bromley MJ (2016) Sterol biosynthesis and azole tolerance is governed by the opposing actions of SrbA and the CCAAT binding complex. PLoS Pathog 12:e1005775. https://doi.org/10.1371/journal.ppat.1005775
Guegan H, Chevrier S, Belleguic C, Deneuville E, Robert-Gangneux F, Gangneux JP (2018) Performance of molecular approaches for Aspergillus detection and azole resistance surveillance in cystic fibrosis. Front Microbiol 9:531. https://doi.org/10.3389/fmicb.2018.00531
Hagiwara D, Watanabe A, Kamei K, Goldman GH (2016) Epidemiological and genomic landscape of azole resistance mechanisms in Aspergillus fungi. Front Microbiol 7:1382. https://doi.org/10.3389/fmicb.2016.01382
Hare RK, Gertsen JB, Astvad KMT, Degn KB, Løkke A, Stegger M, Andersen PS, Kristensen L, Arendrup MC (2019) In vivo selection of a unique tandem repeat mediated azole resistance mechanism TR120 in Aspergillus fumigatus cyp51A, Denmark. Emerg Infect Dis 25:577–580. https://doi.org/10.3201/eid2503.180297
Hillmann F, Novohradska S, Mattern DJ, Forberger T, Heinekamp T, Westermann M, Winckler T, Brakhage AA (2015) Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation. Environ Microbiol 17:2858–2869. https://doi.org/10.1111/1462-2920.12808
Hodiamont CJ, Dolman KM, Ten Berge IJ, Melchers WJ, Verweij PE, Pajkrt D (2009) Multiple-azole-resistant Aspergillus fumigatus osteomyelitis in a patient with chronic granulomatous disease successfully treated with long-term oral posaconazole and surgery. Med Mycol 47:217–220. https://doi.org/10.1080/13693780802545600
Hollomon D (2017) Does agricultural use of azole fungicides contribute to resistance in the human pathogen Aspergillus fumigatus? Pest Manag Sci 73:1987–1993. https://doi.org/10.1002/ps.4607
Howard SJ, Webster I, Moore CB, Gardiner RE, Park S, Perlin DS, Denning DW (2006) Multi-azole resistance in Aspergillus fumigatus. Int J Antimicrob Agents 28:450–453. https://doi.org/10.1016/j.ijantimicag.2006.08.017
Howard SJ, Cerar D, Anderson MJ, Albarrag A, Fisher MC, Pasqualotto AC, Laverdiere M, Arendrup MC, Perlin DS, Denning DW (2009) Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 5:1068–1076. https://doi.org/10.3201/eid1507.090043
Howard SJ, Pasqualotto AC, Denning DW (2010) Azole resistance in allergic bronchopulmonary aspergillosis and Aspergillus bronchitis. Clin Microbiol Infect 16:683–688. https://doi.org/10.1111/j.1469-0691.2009.02911.x
Hurst SF, Berkow EL, Stevenson KL, Litvintseva AP, Lockhart SR (2017) Isolation of azole-resistant Aspergillus fumigatus from the environment in the South-Eastern USA. J Antimicrob Chemother 72:2443–2446. https://doi.org/10.1093/jac/dkx168
Ingham CJ, Kalisman O, Finkelshtein A, Ben-Jacob E (2011) Mutually facilitated dispersal between the nonmotile fungus Aspergillus fumigatus and the swarming bacterium Paenibacillus vortex. Proc Natl Acad Sci U S A 108:19731–19736. https://doi.org/10.1073/pnas.1102097108
Isla G, Leonardelli F, Tiraboschi IN, Refojo N, Hevia A, Vivot W, Szusz W, Cordoba SB, Garcia-Effron G (2018) First clinical isolation of an azole-resistant Aspergillus fumigatus isolate harboring a TR46 Y121F T289A mutation in South America. Antimicrob Agents Chemother 62:e00872-18. https://doi.org/10.1128/AAC.00872-18
Jeanvoine A, Rocchi S, Reboux G, Grenouillet F, Benassarou M, Chirouze C, Millon L (2016) Sinus aspergillosis due to an azole-resistant Aspergillus fumigatus strain carrying the TR34/L98H mutation in immunocompetent host. Infect Dis (Lond) 48:765–766. https://doi.org/10.1080/23744235.2016.1193791
Jeanvoine A, Rocchi S, Reboux G, Crini N, Crini G, Millon L (2017) Azole-resistant Aspergillus fumigatus in sawmills of eastern France. J Appl Microbiol 123:172–184. https://doi.org/10.1111/jam.13488
Jones M (2020) Review of airborne antimicrobial resistance. Report. UK: Environment Agency, Horizon House, Deanery Road, Bristol, BS1 5AH. ISBN: 978-1-84911-424-0. Available online: https://www.gov.uk/government/publications/review-of-airborne-antimicrobial-resistance
Kano R, Kohata E, Tateishi A, Murayama SY, Hirose D, Shibata Y, Kosuge Y, Inoue H, Kamata H, Hasegawa A (2015) Does farm fungicide use induce azole resistance in Aspergillus fumigatus? Med Mycol 53:174–177. https://doi.org/10.1093/mmy/myu076
Kemoi EK, Nyerere A, Bii CC (2018) Triazole-resistant Aspergillus fumigatus from fungicide-experienced soils in Naivasha Subcounty and Nairobi County, Kenya. Int J Microbiol 2018:7147938. https://doi.org/10.1155/2018/7147938
Kidd SE, Goeman E, Meis JF, Slavin MA, Verweij PE (2015) Multi-triazole-resistant Aspergillus fumigatus infections in Australia. Mycoses 58:350–355. https://doi.org/10.1111/myc.12324
Kleinkauf N, Verweij PE, Arendrup MC, Donelly PJ, Cuenca-Estrella M, Fraaije B, Melchers WJG, Adriaenssens N, Kema GHJ, Ullmann A, Bowyer P, Denning DW (2013) European Centre for Disease prevention and Control. Risk assessment on the impact of environmental usage of triazoles on the development and spread of resistance to medical triazoles in Aspergillus species. ECDC, Stockholm. Report available online https://www.ecdc.europa.eu/en/publications-data/risk-assessment-impact-environmental-usage-triazoles-development-and-spread
Komarek M, Cadkova E, Chrastny V, Bordas F, Bollinger JC (2010) Contamination of vineyard soils with fungicides: a review of environmental and toxicological aspects. Environ Int 36:138–151. https://doi.org/10.1016/j.envint.2009.10.005
Korfanty GA, Teng L, Pum N, Xu J (2019) Contemporary gene flow is a major force shaping the Aspergillus fumigatus population in Auckland, New Zealand. Mycopathologia 184:479–492. https://doi.org/10.1007/s11046-019-00361-8
Kourkoumpetis TK, Desalermos A, Muhammed M, Mylonakis E (2012) Central nervous system aspergillosis: a series of 14 cases from a general hospital and review of 123 cases from the literature. Medicine (Baltimore) 91:328–336. https://doi.org/10.1097/MD.0b013e318274cd77
Lamoth F (2016) Aspergillus fumigatus-related species in clinical practice. Front Microbiol 7:683. https://doi.org/10.3389/fmicb.2016.00683
Latgé JP (1999) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12:310–350. https://doi.org/10.1128/CMR.12.2.310
Lavergne RA, Morio F, Favennec L, Dominique S, Meis JF, Gargala G, Verweij PE, Le Pape P (2015) First description of azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation in France. Antimicrob Agents Chemother 59:4331–4335. https://doi.org/10.1128/AAC.00127-15
Lavergne RA, Chouaki T, Hagen F, Toublanc B, Dupont H, Jounieaux V, Meis JF, Morio F, Le Pape P (2017) Home environment as a source of life-threatening azole-resistant Aspergillus fumigatus in immunocompromised patients. Clin Infect Dis 64:76–78. https://doi.org/10.1093/cid/ciw664
Lavergne RA, Morio F, Danner-Boucher I, Horeau-Langlard D, David V, Hagen F, Meis JF, Le Pape P (2019) One year prospective survey of azole resistance in Aspergillus fumigatus at a French cystic fibrosis reference centre: prevalence and mechanisms of resistance. J Antimicrob Chemother 74:1884–1889. https://doi.org/10.1093/jac/dkz144
Lazzarini C, Esposto MC, Prigitano A, Cogliati M, De Lorenzis G, Tortorano AM (2016) Azole resistance in Aspergillus fumigatus clinical isolates from an Italian culture collection. Antimicrob Agents Chemother 60:682–685. https://doi.org/10.1128/AAC.02234-15
Le Pape P, Lavergne RA, Morio F, Alvarez-Moreno C (2016) Multiple fungicide-driven alterations in azole-resistant Aspergillus fumigatus, Colombia, 2015. Emerg Infect Dis 22:156–157. https://doi.org/10.3201/eid2201.150978
Léchenault-Bergerot C, Morin-Crini N, Rocchi S, Lichtfouse E, Chanet G, Crini G (2019) Hemp to limit diffusion of difenoconazole in vegetable garden soils. Heliyon 5:e02392. https://doi.org/10.1016/j.heliyon.2019.e02392
Lee H-J, Cho S-Y, Lee D-G, Park C, Chun H-S, Park Y-J (2018) TR34/L98H mutation in cyp51A gene in Aspergillus fumigatus clinical isolates during posaconazole prophylaxis: first case in Korea. Mycopathologia 183:731–736. https://doi.org/10.1007/s11046-018-0271-8
Leonardelli F, Theill L, Nardin ME, Macedo D, Dudiuk C, Mendez E, Gamarra S, Garcia-Effron G (2017) First itraconazole resistant Aspergillus fumigatus clinical isolate harbouring a G54E substitution in Cyp51Ap in South America. Rev Iberoam Micol 34:46–48. https://doi.org/10.1016/j.riam.2016.05.005
Leroux P, Walker AS (2011) Multiple mechanisms account for resistance to sterol 14alpha-demethylation inhibitors in field isolates of Mycosphaerella graminicola. Pest Manag Sci 67:44–59. https://doi.org/10.1002/ps.2028
Lestrade PP, Bentvelsen RG, Schauwvlieghe A, Schalekamp S, van der Velden W, Kuiper EJ, van Paassen J, van der Hoven B, van der Lee HA, Melchers WJG, de Haan AF, van der Hoeven HL, Rijnders BJA, van der Beek MT, Verweij PE (2019) Voriconazole resistance and mortality in invasive aspergillosis: a multicenter retrospective cohort study. Clin Infect Dis 68:1463–1471. https://doi.org/10.1093/cid/ciy859
Lockhart SR, Frade JP, Etienne KA, Pfaller MA, Diekema DJ, Balajee SA (2011) Azole resistance in Aspergillus fumigatus isolates from the ARTEMIS global surveillance study is primarily due to the TR/L98H mutation in the cyp51A gene. Antimicrob Agents Chemother 55:4465–4468. https://doi.org/10.1128/AAC.00185-11
Lockhart SR, Beer K, Toda M (2020) Azole-resistant Aspergillus fumigatus: what you need to know. Clin Microbiol Newsl 42:1–6. https://doi.org/10.1016/j.clinmicnews.2019.12.003
Mann PA, Parmegiani RM, Wei SQ, Mendrick CA, Li X, Loebenberg D, DiDomenico B, Hare RS, Walker SS, McNicholas PM (2003) Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14alpha-demethylase. Antimicrob Agents Chemother 47:577–581. https://doi.org/10.1128/aac.47.2.577-581.2003
Meis JF, Chowdhary A, Rhodes JL, Fisher MC, Verweij PE (2016) Clinical implications of globally emerging azole resistance in Aspergillus fumigatus. Philos Trans R Soc Lond Ser B Biol Sci 371:1. https://doi.org/10.1098/rstb.2015.0460
Mellado E, Diaz-Guerra TM, Cuenca-Estrella M, Rodriguez-Tudela JL (2001) Identification of two different 14-alpha sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J Clin Microbiol 39:2431–2438. https://doi.org/10.1128/JCM.39.7.2431-2438.2001
Mellado E, Garcia-Effron G, Alcazar-Fuoli L, Cuenca-Estrella M, Rodriguez-Tudela JL (2004) Substitutions at methionine 220 in the 14alpha-sterol demethylase (cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs. Antimicrob Agents Chemother 48:2747–2750. https://doi.org/10.1128/AAC.48.7.2747-2750.2004
Meneau I, Coste AT, Sanglard D (2016) Identification of Aspergillus fumigatus multidrug transporter genes and their potential involvement in antifungal resistance. Med Mycol 54:616–627. https://doi.org/10.1093/mmy/myw005
Montesinos E (2003) Plant-associated microorganisms: a view from the scope of microbiology. Int Microbiol 6:221–223. https://doi.org/10.1007/s10123-003-0141-0
Moore CB, Novak-Frazer L, Muldoon E, Dunn KW, Masania R, Richardson MD, Rautemaa-Richardson R (2017) First isolation of the pan-azole-resistant Aspergillus fumigatus cyp51A TR46/Y121F/T289A mutant in a UK patient. Int J Antimicrob Agents 49:512–514. https://doi.org/10.1016/j.ijantimicag.2017.01.004
Morio F, Aubin GG, Danner-Boucher I, Haloun A, Sacchetto E, Garcia-Hermoso D, Bretagne S, Miegeville M, Le Pape P (2012) High prevalence of triazole resistance in Aspergillus fumigatus, especially mediated by TR/L98H, in a French cohort of patients with cystic fibrosis. J Antimicrob Chemother 67:1870–1873. https://doi.org/10.1093/jac/dks160
Mortensen KL, Mellado E, Lass-Flörl C, Rodriguez-Tudela JL, Johansen HK, Arendrup MC (2010) Environmental study of azole-resistant Aspergillus fumigatus and other aspergilli in Austria, Denmark, and Spain. Antimicrob Agents Chemother 54:4545–4549. https://doi.org/10.1128/AAC.00692-10
Mortensen KL, Jensen RH, Johansen HK, Skov M, Pressler T, Howard SJ, Leatherbarrow H, Mellado E, Arendrup MC (2011) Aspergillus species and other molds in respiratory samples from patients with cystic fibrosis: a laboratory-based study with focus on Aspergillus fumigatus azole resistance. J Clin Microbiol 49:2243–2251. https://doi.org/10.1128/JCM.00213-11
Nawrot U, Kurzyk E, Arendrup MC, Mroczynska M, Wlodarczyk K, Sulik-Tyszka B, Wroblewska M, Ussowicz M, Zdziarski P, Niewinska K, Brillowska-Dabrowska A (2018) Detection of Polish clinical Aspergillus fumigatus isolates resistant to triazoles. Med Mycol 56:121–124. https://doi.org/10.1093/mmy/myx012
O’Gorman CM, Fuller H, Dyer PS (2009) Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus. Nature 457:471–474. https://doi.org/10.1038/nature07528
Onishi K, Muhammad Sarumoh B, Hagiwara D, Watanabe A, Kamei K, Toyotome T (2017) Azole-resistant Aspergillus fumigatus containing a 34-bp tandem repeat in cyp51A promoter is isolated from the environment in Japan. Med Mycol J 23:579–581. https://doi.org/10.3314/mmj.17-00002
Ozmerdiven GE, Ak S, Ener B, Agca H, Cilo BD, Tunca B, Akalin H (2015) First determination of azole resistance in Aspergillus fumigatus strains carrying the TR34/L98H mutations in Turkey. J Infect Chemother 8:581–586. https://doi.org/10.1016/j.jiac.2015.04.012
Pagano L, Akova M, Dimopoulos G, Herbrecht R, Drgona L, Blijlevens N (2011) Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. J Antimicrob Chemother 66:5–14. https://doi.org/10.1093/jac/dkq437
Pelaez T, Gijon P, Bunsow E, Bouza E, Sanchez-Yebra W, Valerio M, Gama B, Cuenca-Estrella M, Mellado E (2012) Resistance to voriconazole due to a G448S substitution in Aspergillus fumigatus in a patient with cerebral aspergillosis. J Clin Microbiol 50:2531–2534. https://doi.org/10.1128/JCM.00329-12
Pelaez T, Monteiro MC, Garcia-Rubio R, Bouza E, Gomez-Lopez A, Mellado E (2015) First detection of Aspergillus fumigatus azole-resistant strain due to cyp51A TR46/Y121F/T289A in an azole-naive patient in Spain. New Microbes New Infect 6:33–34. https://doi.org/10.1016/j.nmni.2015.04.005
Peyton LR, Gallagher S, Hashemzadeh M (2015) Triazole antifungals: a review. Drugs Today (Barc) 51:705–718. https://doi.org/10.1358/dot.2015.51.12.2421058
Pinto E, Monteiro C, Maia M, Faria MA, Lopes V, Lameiras C, Pinheiro D (2018) Aspergillus species and antifungals susceptibility in clinical setting in the north of Portugal: cryptic species and emerging azoles resistance in A. fumigatus. Front Microbiol 9:1656. https://doi.org/10.3389/fmicb.2018.01656
Pontes L, Beraquet CAG, Arai T, Pigolli GL, Lyra L, Watanabe A, Moretti ML, Schreiber AZ (2020) Aspergillus fumigatus clinical isolates carrying cyp51A with TR34/L98H/S297T/F495I substitutions detected after four-year retrospective azole resistance screening in Brazil. Antimicrob Agents Chemother 64:e02059-19. https://doi.org/10.1128/AAC.02059-19
Prigitano A, Venier V, Cogliati M, De Lorenzis G, Esposto MC, Tortorano AM (2014) Azole-resistant Aspergillus fumigatus in the environment of northern Italy, May 2011 to June 2012. Euro Surveill 19:20747. https://doi.org/10.2807/1560-7917.es2014.19.12.20747
Prigitano A, Esposto MC, Biffi A, De Lorenzis G, Favuzzi V, Koncan R, Lo Cascio G, Barao Ocampo M, Colombo C, Pizzamiglio G, Romano L, Tortorano AM (2017) Triazole resistance in Aspergillus fumigatus isolates from patients with cystic fibrosis in Italy. J Cyst Fibros 16:64–69. https://doi.org/10.1016/j.jcf.2016.06.006
Prigitano A, Esposto MC, Romano L, Auxilia F, Tortorano AM (2019) Azole-resistant Aspergillus fumigatus in the Italian environment. J Glob Antimicrob Resist 16:220–224. https://doi.org/10.1016/j.jgar.2018.10.017
Reboux G, Gbaguidi-Haore H, Bellanger AP, Demonmerot F, Houdrouge K, Deconinck E, Bertrand X, Millon L (2014) A 10-year survey of fungal aerocontamination in hospital corridors: a reliable sentinel to predict fungal exposure risk? J Hosp Infect 87:34–40. https://doi.org/10.1016/j.jhin.2014.02.008
Ren J, Jin X, Zhang Q, Zheng Y, Lin D, Yu Y (2017) Fungicides induced triazole-resistance in Aspergillus fumigatus associated with mutations of TR46/Y121F/T289A and its appearance in agricultural fields. J Hazard Mater 326:54–60. https://doi.org/10.1016/j.jhazmat.2016.12.013
Resendiz-Sharpe A, Lagrou K, Meis JF, Chowdhary A, Lockhart SR, Verweij PE (2018) Triazole resistance surveillance in Aspergillus fumigatus. Med Mycol 56:83–92. https://doi.org/10.1093/mmy/myx144
Resendiz-Sharpe A, Mercier T, Lestrade PPA, van der Beek MT, von dem Borne PA, Cornelissen JJ, De Kort E, Rijnders BJA, Schauwvlieghe A, Verweij PE, Maertens J, Lagrou K (2019) Prevalence of voriconazole-resistant invasive aspergillosis and its impact on mortality in haematology patients. J Antimicrob Chemother 74:2759–2766. https://doi.org/10.1093/jac/dkz258
Riat A, Plojoux J, Gindro K, Schrenzel J, Sanglard D (2018) Azole resistance of environmental and clinical Aspergillus fumigatus isolates from Switzerland. Antimicrob Agents Chemother 62:e02088-17. https://doi.org/10.1128/AAC.02088-17
Rocchi S, Daguindau E, Grenouillet F, Deconinck E, Bellanger AP, Garcia-Hermoso D, Bretagne S, Reboux G, Millon L (2014a) Azole-resistant Aspergillus fumigatus isolate with the TR34/L98H mutation in both a fungicide-sprayed field and the lung of a hematopoietic stem cell transplant recipient with invasive aspergillosis. J Clin Microbiol 52:1724–1726. https://doi.org/10.1128/JCM.03182-13
Rocchi S, Reboux G, Larosa F, Scherer E, Daguindeau E, Berceanu A, Deconinck E, Millon L, Bellanger AP (2014b) Evaluation of invasive aspergillosis risk of immunocompromised patients alternatively hospitalized in hematology intensive care unit and at home. Indoor Air 24:652–661. https://doi.org/10.1111/ina.12108
Rocchi S, Poncot M, Morin-Crini N, Laboissiere A, Valot B, Godeau C, Lechenault-Bergerot C, Reboux G, Crini G, Millon L (2018) Determination of azole fungal residues in soils and detection of Aspergillus fumigatus-resistant strains in market gardens of Eastern France. Environ Sci Pollut Res 25:32015–32023. https://doi.org/10.1007/s11356-018-3177-6
Rocchi S, Morin-Crini N, Léchenault-Bergerot C, Godeau C, Fourmentin M, Millon L, Crini G (2019) Effet de l’interaction cyclodextrine-difénoconazole sur la croissance d’une moisissure responsable d’infections fongiques graves, Environnement, Risques & Santé.
Rohr JR, Barrett CB, Civitello DJ, Craft ME, Delius B, DeLeo GA, Hudson PJ, Jouanard N, Nguyen KH, Ostfeld RS, Remais JV, Riveau G, Sokolow SH, Tilman D (2019) Emerging human infectious diseases and the links to global food production. Nat Sustain 2:445–456. https://doi.org/10.1038/s41893-019-0293-3
Schoustra SE, Debets AJM, Rijs A, Zhang J, Snelders E, Leendertse PC, Melchers WJG, Rietveld AG, Zwaan BJ, Verweij PE (2019a) Environmental hotspots for azole resistance selection of Aspergillus fumigatus, the Netherlands. Emerg Infect Dis 25:1347–1353. https://doi.org/10.3201/eid2507.181625
Schoustra SE, Zhang J, Zwaan BJ, Debets AJF, Verweij P, Buijtenhuijs D, Rietveld AG (2019b) New insights in the development of azole-resistance in Aspergillus fumigatus. https://doi.org/10.21945/RIVM-2018-0131
Schwartz S, Ruhnke M, Ribaud P, Corey L, Driscoll T, Cornely OA, Schuler U, Lutsar I, Troke P, Thiel E (2005) Improved outcome in central nervous system aspergillosis, using voriconazole treatment. Blood 106:2641–2645. https://doi.org/10.1182/blood-2005-02-0733
Seufert R, Sedlacek L, Kahl B, Hogardt M, Hamprecht A, Haase G, Gunzer F, Haas A, Grauling-Halama S, MacKenzie CR, Essig A, Stehling F, Sutharsan S, Dittmer S, Killengray D, Schmidt D, Eskandarian N, Steinmann E, Buer J, Hagen F, Meis JF, Rath PM, Steinmann J (2018) Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany. J Antimicrob Chemother 73:2047–2053. https://doi.org/10.1093/jac/dky147
Sewell TR, Zhang Y, Brackin AP, Shelton JMG, Rhodes J, Fisher MC (2019a) Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom. Antimicrob Agents Chemother 63:e00548–e00519. https://doi.org/10.1128/AAC.00548-19
Sewell TR, Zhu J, Rhodes J, Hagen F, Meis JF, Fisher MC, Jombart T (2019b) Nonrandom distribution of azole resistance across the global population of Aspergillus fumigatus. MBio 10:e00392-19. https://doi.org/10.1128/mBio.00392-19
Seyedmousavi S, Hashemi SJ, Zibafar E, Zoll J, Hedayati MT, Mouton JW, Melchers WJ, Verweij PE (2013) Azole-resistant Aspergillus fumigatus, Iran. Emerg Infect Dis 19:832–834. https://doi.org/10.3201/eid1905.130075
Sharma C, Hagen F, Moroti R, Meis JF, Chowdhary A (2015) Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: is it de novo or environmentally acquired? J Glob Antimicrob Res 3:69–73. https://doi.org/10.1016/j.jgar.2015.01.005
Snelders E, van der Lee HAL, Kuijpers J, Rijs AJMM, Varga J, Samson RA, Mellado E, Donders ART, Melchers WJG, Verweij PE (2008) Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5:e219. https://doi.org/10.1371/journal.pmed.0050219
Snelders E, Veld RAGH i’t, Rijs AJMM, Kema GHJ, Melchers WJG, Verweij PE (2009) Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Appl Environ Microbiol 75:4053–4057. https://doi.org/10.1128/AEM.00231-09
Snelders E, Karawajczyk A, Schaftenaar G, Verweij PE, Melchers WJ (2010) Azole resistance profile of amino acid changes in Aspergillus fumigatus cyp51A based on protein homology modeling. Antimicrob Agents Chemother 54:2425–2430. https://doi.org/10.1128/AAC.01599-09
Snelders E, Camps SMT, Karawajczyk A, Schaftenaar G, Kema GHJ, van der Lee HA, Klaassen CH, Melchers WJG, Verweij PE (2012) Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One 7:e31801. https://doi.org/10.1371/journal.pone.0031801
Sułowicz S, Cycoń M, Piotrowska-Seget Z (2016) Non-target impact of fungicide tetraconazole on microbial communities in soils with different agricultural management. Ecotoxicology 25:1047–1060. https://doi.org/10.1007/s10646-016-1661-7
Tangwattanachuleeporn M, Minarin N, Saichan S, Sermsri P, Mitkornburee R, Gross U, Chindamporn A, Bader O (2017) Prevalence of azole-resistant Aspergillus fumigatus in the environment of Thailand. Med Mycol 55:429–435. https://doi.org/10.1093/mmy/myw090
Tashiro M, Izumikawa K, Minematsu A, Hirano K, Iwanaga N, Ide S, Mihara T, Hosogaya N, Takazono T, Morinaga Y, Nakamura S, Kurihara S, Imamura Y, Miyazaki T, Nishino T, Tsukamoto M, Kakeya H, Yamamoto Y, Yanagihara K, Yasuoka A, Tashiro T, Kohno S (2012) Antifungal susceptibilities of Aspergillus fumigatus clinical isolates obtained in Nagasaki, Japan. Antimicrob Agents Chemother 56:584–587. https://doi.org/10.1128/AAC.05394-11
Tilman D, Cassman KG, Matson PA, Naylor R, Polasky S (2002) Agricultural sustainability and intensive production practices. Nature 418:671–677. https://doi.org/10.1038/nature01014
Tornimbene B, Eremin S, Escher M, Griskeviciene J, Manglani S, Pessoa-Silva CL (2018) WHO global antimicrobial resistance surveillance system early implementation 2016–17. Lancet Infect Dis 18:241–242. https://doi.org/10.1016/S1473-3099(18)30060-4
Toyotome T, Fujiwara T, Kida H, Matsumoto M, Wada T, Komatsu R (2016) Azole susceptibility in clinical and environmental isolates of Aspergillus fumigatus from eastern Hokkaido, Japan. J Infect Chemother 22:648–650. https://doi.org/10.1016/j.jiac.2016.03.002
Toyotome T, Hagiwara D, Kida H, Ogi T, Watanabe A, Wada T, Komatsu R, Kamei K (2017) First clinical isolation report of azole-resistant Aspergillus fumigatus with TR34/L98H-type mutation in Japan. J Infect Chemother 23:579–581. https://doi.org/10.1016/j.jiac.2016.12.004
Ullmann AJ, Aguado JM, Arikan-Akdagli S, Denning DW, Groll AH, Lagrou K, Lass-Florl C, Lewis RE, Munoz P, Verweij PE, Warris A, Ader F, Akova M, Arendrup MC, Barnes RA, Beigelman-Aubry C, Blot S, Bouza E, Bruggemann RJM, Buchheidt D, Cadranel J, Castagnola E, Chakrabarti A, Cuenca-Estrella M, Dimopoulos G, Fortun J, Gangneux JP, Garbino J, Heinz WJ, Herbrecht R, Heussel CP, Kibbler CC, Klimko N, Kullberg BJ, Lange C, Lehrnbecher T, Loffler J, Lortholary O, Maertens J, Marchetti O, Meis JF, Pagano L, Ribaud P, Richardson M, Roilides E, Ruhnke M, Sanguinetti M, Sheppard DC, Sinko J, Skiada A, Vehreschild M, Viscoli C, Cornely OA (2018) Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect 24:e1–e38. https://doi.org/10.1016/j.cmi.2018.01.002
van de Veerdonk FL, Gresnigt MS, Romani L, Netea MG, Latge JP (2017) Aspergillus fumigatus morphology and dynamic host interactions. Nat Rev Microbiol 15:661–674. https://doi.org/10.1038/nrmicro.2017.90
Van der Linden J, Snelders E, Kampinga GA, Rijnders BJ, Mattsson E, Debets-Ossenkopp YJ, Kuijper J, Van Tiel FH, Melchers WJ, Verweij PE (2011) Clinical implications of azole resistance in Aspergillus fumigatus, the Netherlands, 2007–2009. Emerg Infect Dis 17:1846–1854. https://doi.org/10.3201/eid1710.110226
van der Linden JW, Camps SM, Kampinga GA, Arends JP, Debets-Ossenkopp YJ, Haas PJ, Rijnders BJ, Kuijper EJ, van Tiel FH, Varga J, Karawajczyk A, Zoll J, Melchers WJ, Verweij PE (2013) Aspergillosis due to voriconazole highly resistant Aspergillus fumigatus and recovery of genetically related resistant isolates from domiciles. Clin Infect Dis 57:513–520. https://doi.org/10.1093/cid/cit320
van Paassen J, Russcher A, Wingerden AW I‘t V-v, Verweij PE, Kuijper EJ (2016) Emerging aspergillosis by azole-resistant Aspergillus fumigatus at an intensive care unit in the Netherlands, 2010–2013. Euro Surveill 21:30300. https://doi.org/10.2807/1560-7917.ES.2016.21.30.30300
Vermeulen E, Maertens J, De Bel A, Nulens E, Boelens J, Surmont I, Mertens A, Boel A, Lagrou K (2015) Nationwide surveillance of azole resistance in Aspergillus diseases. Antimicrob Agents Chemother 59:4569–4576. https://doi.org/10.1128/AAC.00233-15
Verweij PE (2017) Azole-resistance selection in Aspergillus fumigatus, final report. Annex to 27858, No. 411. The Centre for Agriculture and Environment, Laboratory of Genetics of Wageningen University, Department of Medical Microbiology of Radboud University Medical Center. Report available online: https://www.parlementairemonitor.nl/9353000/1/j9vvij5epmj1ey0/vkjwoy3asfzz
Verweij PE, Mellado E, Melchers WJ (2007) Multiple-triazole-resistant aspergillosis. In N Engl J Med 1481–1483. United States. https://doi.org/10.1056/NEJMc061720
Verweij PE, Snelders E, Kema GH, Mellado E, Melchers WJ (2009) Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 9:789–795. https://doi.org/10.1016/S1473-3099(09)70265-8
Verweij PE, Mellado E, Melchers WJ (2017) Multiple-triazole-resistant aspergillosis. N Engl J Med 356:1481–1483. https://doi.org/10.1056/NEJMc061720
Wang HC, Huang JC, Lin YH, Chen YH, Hsieh MI, Choi PC, Lo HJ, Liu WL, Hsu CS, Shih HI, Wu CJ, Chen YC (2018) Prevalence, mechanisms and genetic relatedness of the human pathogenic fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the environment of Taiwan. Environ Microbiol 20:270–280. https://doi.org/10.1111/1462-2920.13988
Wiederhold NP, Patterson TF (2015) Emergence of azole resistance in Aspergillus. Semin Respir Crit Care Med 36:673–680. https://doi.org/10.1055/s-0035-1562894
Wiederhold NP, Garcia Gil V, Gutierrez F, Lindner JR, Albataineh MT, McCarthy DI, Sanders C, Fan H, Fothergill AW, Sutton DA (2015) First detection of TR34/L98H and TR46/Y121F/T289A cyp51 mutations in Aspergillus fumigatus isolates in the United States. J Clin Microbiol 54:168–171. https://doi.org/10.1128/JCM.02478-15
Wu CJ, Wang HC, Lee JC, Lo HJ, Dai CT, Chou PH, Ko WC, Chen YC (2015) Azole-resistant Aspergillus fumigatus isolates carrying TR34/L98H mutations in Taiwan. Mycoses 58:544–549. https://doi.org/10.1111/myc.12354
Zhang J, Snelders E, Zwaan BJ, Schoustra SE, Meis JE, van Dijk K, Hagen F, van der Beek MT, Kampinga GA, Zoll J, Melchers WJG, Verweij PE, Debets AJM (2017) A novel environmental azole resistance mutation in Aspergillus fumigatus and a possible role of sexual reproduction in its emergence. MBio 8:e00791–e00717. https://doi.org/10.1128/mBio.00791-17
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The authors thank Dr. Marc Fourmentin (Université du Littoral Côte-d’Opale, Dunkerque, France) and Marc Maas (The Netherlands) for illustrations graphics. They are also grateful for Benoit Valot (UniversitéBourgogne Franche-Comté, France) for his PubMed data analysis for the world map.
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Rocchi, S., Godeau, C., Crini, G., Snelders, E. (2021). Emergence of a Pathogenic Fungus Resistant to Triazole Antifungal Drugs. In: Morin-Crini, N., Lichtfouse, E., Crini, G. (eds) Emerging Contaminants Vol. 1. Environmental Chemistry for a Sustainable World, vol 65. Springer, Cham. https://doi.org/10.1007/978-3-030-69079-3_3
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