Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?

Verweij, Paul E.; Snelders, Eveline; Kema, G.H.J.; Mellado, Emilia; Melchers, Willem J. G.

doi:10.1016/s1473-3099(09)70265-8

Cited by 534 publications

(530 citation statements)

References 48 publications

Supporting

Mentioning

501

Contrasting

Unclassified

Order By: Relevance

“…120,121 Unsurprisingly, mutations of fungal CYP51, a prime target of the triazoles, seem to mediate the predominant resistance pathways. 122 Large-scale screening for SNPs in relevant human genes, using next-generation sequencing techniques, 123 is now feasible.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

View full text Add to dashboard Cite

“…azole-resistant species in the environment over time (Verweij et al, 2009b). The first case of azole-resistant A. fumigatus was reported in the UK (Denning et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

Nabili

Shokohi

Moazeni

et al. 2016

Journal of Medical Microbiology

View full text Add to dashboard Cite

Triazole antifungal agents are the mainstay of aspergillosis treatment. As highlighted in numerous studies, the global increase in the prevalence of triazole resistance could hamper the management of aspergillosis. In the present three-year study, 513 samples (213 clinical and 300 environmental samples) from 10 provinces of Iran were processed and screened in terms of azole resistance (4 and 1 mg l À1 of itraconazole and voriconazole, respectively), using selective plates. Overall, 150 A. fumigatus isolates (71 clinical and 79 environmental isolates) were detected. The isolates were confirmed by partial sequencing of the b-tubulin gene. Afterwards, in vitro antifungal susceptibility tests against triazole agents were performed, based on the Clinical and Laboratory Standards Institute (CLSI) M38-A2 document. The CYP51A gene was sequenced in order to detect mutations. The MIC of itraconazole against 10 (6.6 %) strains, including clinical (n=3, 4.2 %) and environmental (n=7, 8.8 %) strains, was higher than the breakpoint and epidemiological cut-off value. Based on the findings, the prevalence of azole-resistant A. fumigatus in Iran has increased remarkablyfrom 3.3 % to 6.6 % in comparison with earlier epidemiological research. Among resistant isolates, TR 34 /L98H mutations in the CYP51A gene were the most prevalent (n=8, 80 %), whereas other point mutations (F46Y, G54W, Y121F, G138C, M172V, F219C, M220I, D255E, T289F, G432C and G448S mutations) were not detected. Although the number of patients affected by azole-resistant A. fumigatus isolates was limited, strict supervision of clinical azole-resistant A. fumigatus isolates and persistent environmental screening of azole resistance are vital to the development of approaches for the management of azole resistance in human pathogenic fungi.

show abstract

“…Heavy use of triazole agrofungicides are linked to recent rises in human cases of invasive aspergillosis resistant to antifungal azoles. 11 An example of the limitations of current agrofungicide use is illustrated by Fusarium head blight (FHB)-a destructive and costly disease of wheat, barley and other small grains caused by F. graminearum. 12 There is a serious and persistent need for new agrofungicides that are efficacious, less toxic, cost effective and that do not promote resistance.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

et al. 2010

View full text Add to dashboard Cite

Many Actinomycetes aminoglycosides are widely used antibiotics. Although mainly antibacterials, a few known aminoglycosides also inhibit yeasts, protozoans and important crop pathogenic fungal oomycetes. Here we show that attachment of a C8 alkyl chain to ring III of a neamine-based aminoglycoside specifically at the 4 00 -O position yields a broad-spectrum fungicide (FG08) without the antibacterial properties typical for aminoglycosides. Leaf infection assays and greenhouse studies show that FG08 is capable of suppressing wheat fungal infections by Fusarium graminearum-the causative agent of Fusarium head blight-at concentrations that are minimally phytotoxic. Unlike typical aminoglycoside action of ribosomal protein translation miscoding, FG08's antifungal action involves perturbation of the plasma membrane. This antibacterial to antifungal transformation could pave the way for the development of a new class of aminoglycoside-based fungicides suitable for use in crop disease applications. In addition, this strategy is an example of reviving a clinically obsolete drug by simple chemical modification to yield a new application.

show abstract

Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use?

Cited by 534 publications

References 48 publications

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue?

Antibacterial to antifungal conversion of neamine aminoglycosides through alkyl modification. Strategy for reviving old drugs into agrofungicides

Contact Info

Product

Resources

About