Understanding the environmental drivers of clinical azole resistance in Aspergillus species

Abstract

 Aspergilli are ubiquitous fungal pathogens associated with severe life-threatening infections, especially in immunocompromised patients. Azoles are the first line of defence in the fight against most Aspergillus -related infections. However, resistance to these therapeutic compounds has developed, which is mainly due to the existence of mutations in lanosterol 14 alpha-demethylase (Cyp51A), a crucial enzyme in the pathway that produces ergosterol and is the target of azole antifungals. Azole-based antifungal medications are ineffective because of infections brought on by azole-resistant Aspergillus  species, leading to a high fatality rate. However, resistant Aspergillus  isolates have also been isolated from azole-naïve patients. Global agricultural practices promote the use of azole fungicides to protect crops from phytopathogens. Usage of azole fungicides on a large scale has been linked to the development of resistance among Aspergillus  species prevalent in the environment. The infections caused by these azoleresistant Aspergillus  species cannot be treated by the available azole drugs, in turn leading to high morbidity and mortality rates. Thus, knowledge of the environmental drivers and comprehending the genetic basis of fungal drug resistance evolution is pertinent, considering increasing numbers of patients with COVID-19 infections who are sensitive to opportunistic fungal infections. This article emphasises the prevalence and underlying mechanisms of azole resistance in Aspergillus  species, with a focus on environmental triggers and resistance development. It also highlights the need for regular surveillance of pesticide use in agriculture, detection of triazole-resistant Aspergillus  species in environmental and clinical settings and development of new antifungal drugs.