Abstract
Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.
Highlights
Aspergillus spp. are opportunistic fungi that cause both allergic and invasive syndromes
There were no major differences in susceptibility to amphotericin B (AmB) except for one strain (CM8087) that could be considered AmB resistant
Cyp51Cwas expressed in very low levels, we observed a significant increase of gene expression for all strains relative to the ATCC2004304 (Figure 1)
Summary
Aspergillus spp. are opportunistic fungi that cause both allergic and invasive syndromes. Aspergillus contains approximately 175 species, but only a few of them have been associated with human disease [1]. The primary route of infection is characterized by the inhalation of conidia which, due to their small size, reach the pulmonary alveoli and cause local and invasive infections [2]. Among the wide range of aspergillosis manifestations, invasive aspergillosis (IA) is the most severe one and is linked to high morbidity and mortality rates in immunocompromised patients [3,4,5]. Besides the risk of immunosuppressed patients to Aspergillus infections, sporadic cases of invasive aspergillosis on immunocompetent hosts have been reported [6,7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
