other available antimycotics, they are applied not only to prevent but also to treat
plant fungal diseases. Triazoles have also been shown to promote the growth of plant
leading to increase in the crop yield [410, 411].
In the medical field, synthetic antifungal agents are widely used for the treatment
and prophylaxis of many mycoses [412]. As a consequence of their common use,
substantial amounts of azoles reach the wastewater treatment plants [413–
416]. There, as observed for many other PhACs, due to their intrinsic stability,
triazoles can remain stable and active with only slight changes in their chemical
structure. Studies investigating the occurrence of azole fungicides in wastewater are
limited [413, 414, 417–419]. However, a number of studies have identified wastewater effluents as triazole pollution point source of surface waters and agricultural
soil [134, 420–425].
The dissipation of triazole plant protection fungicides in soils has been widely
documented. Pesticides such as tebuconazole [426–433], epoxiconazole [434, 435],
propiconazole [436–438] and cyproconazole [439] have been shown to be relatively
persistent in soil. In soil tebuconazole was shown to be transformed in 34 different
transformation products [440]. To date Burkholderia sp. and Pseudomonas
aeruginosa are the only two soil bacterial isolates known to degrade the fungicide
propiconazole [441, 442].
Similarly, antifungal medicines are highly resistant to microbial degradation.
Experiments performed in soil microcosms showed that fluconazole and clotrimazole were scarcely degraded, with half-lives in the range of 73 to 85 days for
fluconazole and of 29 to 126 days or of 36.2 to 130.8 days for clotrimazole
[135, 136]. In field conditions, a higher persistence was found in biosolid amended
soils for the azole biocides climbazole, clotrimazole, and miconazole [25, 131, 134],
with differences in dissipation half-lives attributed to soil types and biosolid application rates. To date, only one study has reported the ability of one edible fungal
specie to degrade bifonazole and clotrimazole [443].
As observed with antibiotics, the intensive and repeated use of triazoles has led to
the emergence of fungal resistances. Among the different mechanisms of resistance
involved, the overexpression of the CYP51 gene that codes for the lanosterol
14α-demethylase, due to mutations (insertions or duplications) in the promoter
region, and the increase in molecular efflux by ABC (ATP-binding cassette) transporters caused by the overexpression of genes coding for membrane transport have
been mainly observed [407, 444–446]. Clinical isolates with observed resistance to
triazoles include the species of Aspergillus, Candida, Fusarium, Zygomycetes,
Trichosporon, Penicillium, Bipolaris, and Scedosporium, among others [447–
452]. The majority of cases of azole-resistant diseases are due to resistant Aspergillus
fumigatus which causes a variety of diseases in humans and animals ranging from
allergic, chronic, and acute invasive diseases, the latter posing a significant threat to
immunocompromised patients [453]. The surge of resistant fungi of human pathogens in the medical field has been related to the exposure to fungicides used in
agroecosystems [454–456]. The important use of triazoles in agriculture may indeed
exert a selective pressure favoring the survival of certain human pathogenic fungi,
increasing the risks and chances for humans to encounter such resisting microbes.
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S. Gallego and F. Martin-Laurent
plant fungal diseases. Triazoles have also been shown to promote the growth of plant
leading to increase in the crop yield [410, 411].
In the medical field, synthetic antifungal agents are widely used for the treatment
and prophylaxis of many mycoses [412]. As a consequence of their common use,
substantial amounts of azoles reach the wastewater treatment plants [413–
416]. There, as observed for many other PhACs, due to their intrinsic stability,
triazoles can remain stable and active with only slight changes in their chemical
structure. Studies investigating the occurrence of azole fungicides in wastewater are
limited [413, 414, 417–419]. However, a number of studies have identified wastewater effluents as triazole pollution point source of surface waters and agricultural
soil [134, 420–425].
The dissipation of triazole plant protection fungicides in soils has been widely
documented. Pesticides such as tebuconazole [426–433], epoxiconazole [434, 435],
propiconazole [436–438] and cyproconazole [439] have been shown to be relatively
persistent in soil. In soil tebuconazole was shown to be transformed in 34 different
transformation products [440]. To date Burkholderia sp. and Pseudomonas
aeruginosa are the only two soil bacterial isolates known to degrade the fungicide
propiconazole [441, 442].
Similarly, antifungal medicines are highly resistant to microbial degradation.
Experiments performed in soil microcosms showed that fluconazole and clotrimazole were scarcely degraded, with half-lives in the range of 73 to 85 days for
fluconazole and of 29 to 126 days or of 36.2 to 130.8 days for clotrimazole
[135, 136]. In field conditions, a higher persistence was found in biosolid amended
soils for the azole biocides climbazole, clotrimazole, and miconazole [25, 131, 134],
with differences in dissipation half-lives attributed to soil types and biosolid application rates. To date, only one study has reported the ability of one edible fungal
specie to degrade bifonazole and clotrimazole [443].
As observed with antibiotics, the intensive and repeated use of triazoles has led to
the emergence of fungal resistances. Among the different mechanisms of resistance
involved, the overexpression of the CYP51 gene that codes for the lanosterol
14α-demethylase, due to mutations (insertions or duplications) in the promoter
region, and the increase in molecular efflux by ABC (ATP-binding cassette) transporters caused by the overexpression of genes coding for membrane transport have
been mainly observed [407, 444–446]. Clinical isolates with observed resistance to
triazoles include the species of Aspergillus, Candida, Fusarium, Zygomycetes,
Trichosporon, Penicillium, Bipolaris, and Scedosporium, among others [447–
452]. The majority of cases of azole-resistant diseases are due to resistant Aspergillus
fumigatus which causes a variety of diseases in humans and animals ranging from
allergic, chronic, and acute invasive diseases, the latter posing a significant threat to
immunocompromised patients [453]. The surge of resistant fungi of human pathogens in the medical field has been related to the exposure to fungicides used in
agroecosystems [454–456]. The important use of triazoles in agriculture may indeed
exert a selective pressure favoring the survival of certain human pathogenic fungi,
increasing the risks and chances for humans to encounter such resisting microbes.
280
S. Gallego and F. Martin-Laurent