Abstract
Invasive aspergillosis is a life-threatening mycosis caused by the pathogenic fungus Aspergillus. The predominant causal species is Aspergillus fumigatus, and azole drugs are the treatment of choice. Azole drugs approved for clinical use include itraconazole, voriconazole, posaconazole, and the recently added isavuconazole. However, epidemiological research has indicated that the prevalence of azole-resistant A. fumigatus isolates has increased significantly over the last decade. What is worse is that azole-resistant strains are likely to have emerged not only in response to long-term drug treatment but also because of exposure to azole fungicides in the environment. Resistance mechanisms include amino acid substitutions in the target Cyp51A protein, tandem repeat sequence insertions at the cyp51A promoter, and overexpression of the ABC transporter Cdr1B. Environmental azole-resistant strains harboring the association of a tandem repeat sequence and punctual mutation of the Cyp51A gene (TR34/L98H and TR46/Y121F/T289A) have become widely disseminated across the world within a short time period. The epidemiological data also suggests that the number of Aspergillus spp. other than A. fumigatus isolated has risen. Some non-fumigatus species intrinsically show low susceptibility to azole drugs, imposing the need for accurate identification, and drug susceptibility testing in most clinical cases. Currently, our knowledge of azole resistance mechanisms in non-fumigatus Aspergillus species such as A. flavus, A. niger, A. tubingensis, A. terreus, A. fischeri, A. lentulus, A. udagawae, and A. calidoustus is limited. In this review, we present recent advances in our understanding of azole resistance mechanisms particularly in A. fumigatus. We then provide an overview of the genome sequences of non-fumigatus species, focusing on the proteins related to azole resistance mechanisms.
Highlights
The incidence of fungal infection has increased over the past three decades (Denning, 1998; Dasbach et al, 2000; Kousha et al, 2011; Suzuki et al, 2013; Bitar et al, 2014)
As azole resistance is correlated with aspergillosis treatment failure (Howard et al, 2009), a number of studies have focused on the epidemiology, molecular mechanisms, and diagnostic methods relating to this type of resistance
Another emerging issue in the pathology of aspergillosis is that non-fumigatus species are being increasingly identified as causal agents of invasive aspergillosis; these include A. flavus, A. niger, A. terreus, and A. calidoustus as well as other Aspergillus species that belong to Aspergillus section Fumigati (Baddley et al, 2009; Balajee et al, 2009; Krishnan et al, 2009; Tashiro et al, 2011)
Summary
The incidence of fungal infection has increased over the past three decades (Denning, 1998; Dasbach et al, 2000; Kousha et al, 2011; Suzuki et al, 2013; Bitar et al, 2014). As azole resistance is correlated with aspergillosis treatment failure (Howard et al, 2009), a number of studies have focused on the epidemiology, molecular mechanisms, and diagnostic methods relating to this type of resistance Another emerging issue in the pathology of aspergillosis is that non-fumigatus species are being increasingly identified as causal agents of invasive aspergillosis; these include A. flavus, A. niger, A. terreus, and A. calidoustus as well as other Aspergillus species that belong to Aspergillus section Fumigati (Baddley et al, 2009; Balajee et al, 2009; Krishnan et al, 2009; Tashiro et al, 2011). This study proposed the ECVs (itraconazole, voriconazole, and posaconazole) for other Aspergillus species including A. flavus (1, 1, and 0.25 mg/L), A. terreus (1, 1, and 0.5 mg/L), A. niger (2, 2, and 0.5 mg/L), and A. nidulans (1, 2, and 1 mg/L; Espinel-Ingroff et al, 2010) These ECV data could help to characterize Aspergillus isolates and to monitor the emergence of azole-resistant strains by in vitro antifungal susceptibility testing with CLSI BMD method. A research group from the Netherlands most recently published a survey of azole-resistant A. fumigatus, in which 364 of 952 clinical strains (38.2%) isolated by, or referred to, the laboratory from 2010 to 2013 were
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
