Abstract
Amphotericin B (AMB) is a major fungicidal polyene agent that has a broad spectrum of action against invasive fungal infections. AMB is typically used as the last-line drug against serious and life-threatening infections when other drugs have failed to eliminate the fungal pathogens. Recently, AMB resistance in Aspergillus fumigatus has become more evident. For example, a high rate of AMB resistance (96%) was noted in the A. fumigatus population in Hamilton, Ontario, Canada. AMB-resistant strains have also been found in other countries. However, the mechanism of AMB resistance remains largely unknown. Here, we investigated the potential genes and mutations associated with AMB resistance using whole-genome sequences and examined AMB resistance distribution among genetic populations. A total of 196 whole-genome sequences representing strains from 11 countries were examined. Analyses of single nucleotide polymorphisms (SNPs) at the whole-genome level revealed that these strains belonged to three divergent genetic clusters, with the majority (90%) of AMB resistant strains located in one of the three clusters, Cluster 2. Our analyses identified over 60 SNPs significantly associated with AMB resistance. Together, these SNPs represent promising candidates from which to investigate the putative molecular mechanisms of AMB resistance and for their potential use in developing rapid diagnostic markers for clinical screening of AMB resistance in A. fumigatus.
Highlights
Aspergillus fumigatus is a globally distributed saprophytic mold that plays a major role in recycling environmental carbon and nitrogen
CON4 was susceptible to amphotericin B (AMB), with an minimum inhibitory concentration (MIC) of 1 mg/L, and CM21 had an intermediate resistance at 2 mg/L
The results showed that our strains were divided into 3 clusters (Figure 3A), similar to results based on all 196 strains
Summary
Aspergillus fumigatus is a globally distributed saprophytic mold that plays a major role in recycling environmental carbon and nitrogen. The fungus has an abundant asexual reproduction cycle and produces a prolific number of asexual spores, known as conidia [1]. The conidia’s hydrophobic surface facilitates air dispersion and the spores can remain dormant and/or germinate in a wide range of environmental conditions [2]. A. fumigatus has a ubiquitous presence in the air that can reach up to conidia/m3 in certain environments [3]. Population genetic studies using simple sequence repeat (SSR) markers suggest that airborne dispersal by conidia has likely played a major role in the global population structure of A. fumigatus [4,5]. Whether the genetic uniqueness of geographic samples based on certain
Sign-in/Register to view highlights & summary 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.
