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Environmental Science and Pollution Research

, Volume 25, Issue 32, pp 32015–32023 | Cite as

Determination of azole fungal residues in soils and detection of Aspergillus fumigatus-resistant strains in market gardens of Eastern France

  • Steffi RocchiEmail author
  • Manon Ponçot
  • Nadia Morin-Crini
  • Audrey Laboissière
  • Benoit Valot
  • Chloé Godeau
  • Clothilde Léchenault-Bergerot
  • Gabriel Reboux
  • Grégorio Crini
  • Laurence Millon
Research Article

Abstract

Medical azole antifungals are major compounds used to prevent and to treat invasive aspergillosis (IA). Azole fungicides, called DMI (14-alpha demethylase inhibitors), are also widely used for crop protection and have been reported to be linked to azole-resistant A. fumigatus (aR-Af) development in the environment. The aim of this study was to determine whether or not market gardens that spray DMIs in Eastern France are also affected by the presence of aR-Af. Forty aR-Afs were detected in soils in only two of the four market gardens using DMIs, with 23% (7/30) and 10% (3/30) of soils containing aR-Af. A total of 87.5% of these isolates had the TR34/L98H mutation and 22.5% the TR46/Y121F/T289A mutation on the cyp51A gene. Analyses of residual azole concentrations in soils showed the presence of difenoconazole for up to 2 years after spraying, but only in soils of market gardens where aR-Af was detected. It is very important to identify professional activities that could lead to aR-Af development and to develop preventive measures for at-risk patients living near professional activities using DMIs. We have to better understand why, in some cases, the use of DMI is not linked to aR-Af. Measures should be taken to avoid the use of DMI conferring cross-resistance to preserve the efficiency of human therapeutics.

Keywords

DMI fungicides Aspergillus fumigatus resistance Market gardens TR34/L98H mutation TR46/Y121F/T289A mutation Selection pressure 

Notes

Acknowledgments

We are grateful to Pamela Albert for her editorial assistance. The work was financially supported by LTSER Zone Atelier Arc Jurassien and the Observatoire des Sciences de l’Univers Terre Homme Environnement Temps Astronomie de Franche-Comté-Bourgogne. We thank market gardeners who participated in this study.

DFC difenoconazole, NA not available

LD limit of detection (4.2 ng g−1)

Supplementary material

11356_2018_3177_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 19 kb)

References

  1. Alanio A, Sitterle E, Liance M, Farrugia C, Foulet F, Botterel F, Hicheri Y, Cordonnier C, Costa JM, Bretagne S (2011) Low prevalence of resistance to azoles in Aspergillus fumigatus in a French cohort of patients treated for haematological malignancies. J Antimicrob Chemother 66:371–374CrossRefGoogle Scholar
  2. Alvarez-Moreno C, Lavergne RA, Hagen F, Morio F, Meis JF, Le Pape P (2017): Azole-resistant Aspergillus fumigatus harboring TR(34)/L98H, TR(46)/Y121F/T289A and TR(53) mutations related to flower fields in Colombia. Sci rep 7Google Scholar
  3. Arendrup MC, Mavridou E, Mortensen KL, Snelders E, Frimodt-Møller N, Khan H, Melchers WJ, Verweij PE (2010) Development of azole resistance in Aspergillus fumigatus during azole therapy associated with change in virulence. PLoS One 5:e10080CrossRefGoogle Scholar
  4. Arendrup MC, Cuenca-Estrella M, Lass-Florl C, Hope WW (2012) EUCAST technical note on Aspergillus and amphotericin B, itraconazole, and posaconazole. Clin Microbiol Infect 18:E248–E250CrossRefGoogle Scholar
  5. Ashu EE, Kim GY, Roy-Gayos P, Dong K, Forsythe A, Giglio V, Korfanty G, Yamamura D, Xu J (2018) Limited evidence of fungicide-driven triazole-resistant Aspergillus fumigatus in Hamilton, Canada. Can J Microbiol 64:119–130CrossRefGoogle Scholar
  6. 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 56:659–663CrossRefGoogle Scholar
  7. Baharoglu Z, Mazel D (2014) SOS, the formidable strategy of bacteria against aggressions. FEMS Microbiol Rev 38:1126–1145CrossRefGoogle Scholar
  8. Berger S, El Chazli Y, Babu AF, Coste AT (2017) Azole resistance in Aspergillus fumigatus: a consequence of antifungal use in agriculture? Front Microbiol 8:1024CrossRefGoogle Scholar
  9. Bruvo R, Michiels NK, D'Souza TG, Schulenburg H (2004) A simple method for the calculation of microsatellite genotype distances irrespective of ploidy level. Mol Ecol 13:2101–2106CrossRefGoogle Scholar
  10. 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: 10–16CrossRefGoogle Scholar
  11. Chowdhary A, Sharma C, van den Boom M, Yntema JB, Hagen F, Verweij PE, Meis JF (2014) Multi-azole-resistant Aspergillus fumigatus in the environment in Tanzania. J Antimicrob ChemotherGoogle Scholar
  12. 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 6:428CrossRefGoogle Scholar
  13. Denning DW, Bowyer P (2013) Voriconazole resistance in Aspergillus fumigatus: should we be concerned? Clin Infect Dis, United States 57:521–523CrossRefGoogle Scholar
  14. Denning DW, Venkateswarlu K, Oakley KL, Anderson MJ, Manning NJ, Stevens DA, Warnock DW, Kelly SL (1997) Itraconazole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother 41:1364–1368CrossRefGoogle Scholar
  15. Garcia-Rubio R, Cuenca-Estrella M, Mellado E (2017) Triazole resistance in Aspergillus species: an emerging problem. Drugs 77:599–613CrossRefGoogle Scholar
  16. Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, Roilides E, Styczynski J, Warris A, Lehrnbecher T (2014) Fourth European conference on infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation. Lancet Oncol 15:e327–e340CrossRefGoogle Scholar
  17. Hope WW, Cuenca-Estrella M, Lass-Florl C, Arendrup MC (2013) EUCAST technical note on voriconazole and Aspergillus spp. Clin Microbiol Infect 19:E278–E280CrossRefGoogle Scholar
  18. 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 15:1068–1076CrossRefGoogle Scholar
  19. 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) 48:765–766CrossRefGoogle Scholar
  20. 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 CrossRefGoogle Scholar
  21. Kamvar ZN, Brooks JC, Grünwald NJ (2015) Novel R tools for analysis of genome-wide population genetic data with emphasis on clonality. Front Genet 6:208CrossRefGoogle Scholar
  22. 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 36:138–151CrossRefGoogle Scholar
  23. 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 59:4331–4335CrossRefGoogle Scholar
  24. 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: 1846–1854Google Scholar
  25. 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 371:20150460CrossRefGoogle Scholar
  26. 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 39:2431–2438CrossRefGoogle Scholar
  27. 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: 20747Google Scholar
  28. 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 326:54–60CrossRefGoogle Scholar
  29. Rocchi S, Daguindau E, Grenouillet F, Deconinck E, Bellanger AP, Garcia-Hermoso D, Bretagne S, Reboux G, Millon L (2014) 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 52:1724–1726CrossRefGoogle Scholar
  30. 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? Journal of Global Antimicrobial Resistance 3:69–74CrossRefGoogle Scholar
  31. 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: e219Google Scholar
  32. Snelders E, Huis in’t Veld RAG, Rijs AJMM, Kema GHJ, Melchers WJG, Verweij PE (2009) Possible environmental origin of resistance of Aspergillus fumigatus to medical triazoles. Applied and Environmental Microbiology 75:4053–4057CrossRefGoogle Scholar
  33. 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: e31801CrossRefGoogle Scholar
  34. Snelders E, Camps SM, Karawajczyk A, Rijs AJ, Zoll J, Verweij PE, Melchers WJ (2015) Genotype-phenotype complexity of the TR46/Y121F/T289A cyp51A azole resistance mechanism in Aspergillus fumigatus. Fungal Genet Biol 82:129–135CrossRefGoogle Scholar
  35. Sweileh WM, Sawalha AF, Al-Jabi S, Zyoud SH (2017) Bibliometric analysis of literature on antifungal triazole resistance: 1980 - 2015. Germs 7:19–27CrossRefGoogle Scholar
  36. Tissot F, Agrawal S, Pagano L, Petrikkos G, Groll AH, Skiada A, Lass-Florl C, Calandra T, Viscoli C, Herbrecht R (2017) ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica 102:433–444CrossRefGoogle Scholar
  37. de Valk HA, Meis JF, Curfs IM, Muehlethaler K, Mouton JW, Klaassen CH (2005) Use of a novel panel of nine short tandem repeats for exact and high-resolution fingerprinting of Aspergillus fumigatus isolates. J Clin Microbiol 43: 4112–4120Google Scholar
  38. Zhang J, van den Heuvel J, Debets AJM, Verweij PE, Melchers WJG, Zwaan BJ, Schoustra SE (2017) Evolution of cross-resistance to medical triazoles in Aspergillus fumigatus through selection pressure of environmental fungicides. Proc Biol Sci 284, 20170635Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Steffi Rocchi
    • 1
    • 2
    Email author return OK on get
  • Manon Ponçot
    • 2
  • Nadia Morin-Crini
    • 2
  • Audrey Laboissière
    • 2
  • Benoit Valot
    • 2
  • Chloé Godeau
    • 2
  • Clothilde Léchenault-Bergerot
    • 2
  • Gabriel Reboux
    • 1
    • 2
  • Grégorio Crini
    • 2
  • Laurence Millon
    • 1
    • 2
  1. 1.Parasitology-Mycology DepartmentUniversity HospitalBesançonFrance
  2. 2.Chrono-Environnement UMR 6249 CNRS, Bourgogne Franche-Comté UniversityBesançonFrance

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