Antifungal azoles and azole resistance in the environment: current status and future perspectives—a review

Abstract

Following their extensive use, azole antifungals may enter the environment through the discharge of domestic, industrial and hospital wastewaters, agricultural runoffs and as leachates in wastedisposal sites. The presence of the azole antifungals poses potential toxicity risks to non-target organisms and plays a critical role in the evolution and/or selection of azole resistant fungal strains in the environment. Toxicities such as inhibition of algal growth, endocrine disruption in fish, CYP450-effected steroidogenesis, modulating sex differentiation in frogs, and reduction of larval body mass and growth rate have been related to azole antifungals. In addition, the isolation of azole resistant fungi such as Aspergillus fumigatus in both the environment and clinic retaining similar mode of molecular drug resistance mechanism has drawn the attention of many researchers. Therefore, the investigation of the occurrence and distribution of azole antifungals as well as azole resistant environmental isolates of fungi is becoming a trendy research venue. Here we review the occurrence of antifungal azoles and azole resistance in the environment. The major points discussed are (1) an update on the environmental occurrence, distribution and ecological risks of the most commonly used azole antifungals in the environment including surface water and drinking water (2) environmental azole antifungal resistance, predominant molecular mechanisms of azole resistance in the environment, and the implications for human health (3) future trends and perspectives that could help reduce the ecological and human health risks of azoles and tackle the spread of azole resistance in the environment, and hence in the clinic.

Antifungal activity of linalool against fluconazole-resistant clinical strains of vulvovaginal Candida albicans and its predictive mechanism of action

“…Currently, topical fluconazole and imidazole drugs are preferred as first-line agents; however, due to the adverse effects, high costs, and strain resistance to the antifungals, alternatives to these treatments should be considered ( 7 ). Regarding cellular mechanisms of antifungal resistance to azoles and imidazoles, several studies agree that this phenomenon is mainly due to amino acid substitutions in the pharmacological target and overexpression of the ERG 11 gene encoding the lanosterol 14α-demethylase enzyme in C. albicans ( 8 ). Thus, the pharmacological study of molecules, especially natural ones with antifungal potential, may constitute a possible therapeutic alternative for the treatment of CVV ( 9 ).…”

Antifungal Exposure and Resistance Development: Defining Minimal Selective Antifungal Concentrations and Testing Methodologies

“…Furthermore, reclaimed wastewater is also increasingly recycled for irrigation purposes, potentially increasing the contamination of agricultural land with antifungals not efficiently removed during treatment ( Calderon-Preciado et al., 2011 ; Chen et al., 2011 ). Effluent from pharmaceutical factories ( Liu and Wong, 2013 ; Assress et al., 2021a ) and waste from industrial applications [e.g., anti-fouling paints ( Andersson Trojer et al., 2013 )] have also been highlighted as environmental sources of antifungals.…”

<i>CDR1, CDR2, MDR1</i> and <i>ERG11</i> expression in azole resistant <i>Сandida albicans</i> isolated from HIV-infected patients in city of Moscow

“…Гиперэкспрессия гена ERG11, ответственного за синтез фермента-мишени азолов, наблюдалась у 35% штаммов [28]. В швейцарском исследовании на 16 изолятах C. albicans от пациентов со СПИД выявлено преобладание гиперэкспрессии CDR1 и MDR1 [5]. В исследовании, проведенном в Сингапуре в 2012-2015 гг., у всех изолятов C. albicans обнаружена повышенная экспрессия CDR2, у двух штаммов -повышенная экспрессия MDR1 [38].…”