Widely dispersed clonal expansion of multi-fungicide-resistant Aspergillus fumigatus limits genomic epidemiology prospects
Widely dispersed clonal expansion of multi-fungicide-resistant Aspergillus fumigatus limits genomic epidemiology prospects Eveline Snelders
mBio. 2025 May 20:e0365224. doi: 10.1128/mbio.03652-24. Online ahead of print.
ABSTRACT
Invasive aspergillosis, caused by Aspergillus fumigatus, represents a critical public health concern, particularly due to increasing resistance to triazole antifungals linked to TR34/TR46 cyp51A haplotypes. In our genomic epidemiology study of 157 A. fumigatus isolates from Dutch environmental hotspots and two clinical centers, we identified near-identical genomes in several environmental and patient isolates, indicating a probable link. However, the geographic and temporal data alone are not sufficient to explain direct transmission pathways. Furthermore, a comparison with more than 1,200 globally sourced genomes revealed the extensive dissemination of certain clonal groups across multiple distant regions, raising significant challenges for the utility of genomic epidemiology. The discovery of high genetic diversity and the widespread distribution of some clonal groups challenges current understanding, suggesting that in most cases, tracing the precise source of individual infections will remain extremely difficult, even with increased sampling. In addition, we uncovered that the multi-triazole-resistant TR34/TR46 cyp51A haplotypes are associated with resistance to non-triazole fungicides such as benzimidazole, succinate dehydrogenase inhibitor, and quinone outside inhibitor classes, strongly suggesting an exposure history to multiple agricultural fungicides in these environmental hotspots. This resistance beyond the azole class suggests that strategies targeting only triazoles may be insufficient. Our findings challenge current paradigms and carry significant implications for One Health research and global public health strategies, underscoring the urgency of multidisciplinary approaches to tracking and monitoring fungal resistance.IMPORTANCEOur study links triazole-resistant A. fumigatus isolates cultured from three environmental hotspots to cases of aspergillus disease in two hospitals in the Netherlands. Genome comparisons of isolates from environmental hotspots and patients showed multiple near-identical linked genotypes, consistent with a route of transmission from the environment to patients. Linked cases without clear transmission routes emphasize the need to better understand the ecology of this fungus. Since patients often do not visit rural hotspots, research should explore complex, long-distance transmission mechanisms, including airborne dispersal of conidia or non-agricultural habitats. The multi-fungicide resistance phenotype suggests reducing one class of fungicides alone may not lower resistance selection. Instead, interventions should target modifying environments that promote the growth of fungicide-resistant A. fumigatus and prevent the escape of resistant spores from these hotspots to mitigate the burden of environmental resistance effectively.
PMID:40391955 | DOI:10.1128/mbio.03652-24
Invasive aspergillosis, caused by Aspergillus fumigatus, represents a critical public health concern, particularly due to increasing resistance to triazole antifungals linked to TR(34)/TR(46) cyp51A haplotypes. In our genomic epidemiology study of 157 A. fumigatus isolates from Dutch environmental hotspots and two clinical centers, we identified near-identical genomes in several environmental and patient isolates, indicating a probable link. However, the geographic and temporal data alone are… [#item_author]