Contemporary Gene Flow is a Major Force Shaping the Aspergillus fumigatus Population in Auckland, New Zealand

Korfanty, Greg; Teng, Lilly; Pum, Nicole; Xu, Jianping

doi:10.1007/s11046-019-00361-8

Cited by 16 publications

(31 citation statements)

References 49 publications

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“…However, most of these insertional mutations were also associated with amino acid substitution mutations, similar to what we found here. For example, the most frequent mutation found in our study, TR 34 /L98H (n = 25; 76%), was also the most frequently found in India and the Netherlands (47,60). A mutation found in our sample, TR 46 /Y121F/T289A (n = 3; 9%), was the most frequently found in flower fields in Colombia (n = 17; 80.9%), where the proportion of TR 34 /L98H accounted for only 4.8% (1/21) of the azole-resistant isolates (64).…”

Section: Resultssupporting

confidence: 52%

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Extensive Genetic Diversity and Widespread Azole Resistance in Greenhouse Populations of Aspergillus fumigatus in Yunnan, China

Zhou

Korfanty

et al. 2021

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Aspergillus fumigatus is the main cause of invasive aspergillosis (IA) with a high annual global incidence and mortality rate. Recent studies have indicated an increasing prevalence of azole-resistant A. fumigatus (ARAF) strains, with agricultural use of azole fungicides as a potential contributor. China has an extensive agricultural production system and uses a wide array of fungicides for crop production, including in modern growth facilities such as greenhouses. Soils in greenhouses are among the most intensively cultivated. However, little is known about the occurrence and distribution of ARAF in greenhouse soils. Here, we investigated genetic variation and triazole drug susceptibility in A. fumigatus from greenhouses around metropolitan Kunming in Yunnan, southwest China. Abundant allelic and genotypic variations were found among 233 A. fumigatus strains isolated from nine greenhouses in this region. Significantly, ∼80% of the strains were resistant to at least one medical triazole drug, with >30% showing cross-resistance to both itraconazole and voriconazole. Several previously reported mutations associated with triazole resistance in the triazole target gene cyp51A were also found in our strains, with a strong positive correlation between the frequency of mutations at the cyp51A promoter and that of voriconazole resistance. Phylogenetic analyses of cyp51A gene sequences showed evidence for multiple independent origins of azole-resistant genotypes of A. fumigatus in these greenhouses. Evidence for multiple origins of azole resistance and the widespread distributions of genetically very diverse triazole-resistant strains of A. fumigatus in greenhouses calls for significant attention from public health agencies. IMPORTANCE The origin and prevalence of azole-resistant Aspergillus fumigatus have been attracting increasing attention from biologists, clinicians, and public health agencies. Current evidence suggests agricultural fungicide use as a major cause. In southwest China, greenhouses are used to produce large amounts of fruits, flowers, and vegetables for consumers throughout China as well as those in other countries, primarily in southeast Asia. Here, we found a very high frequency (∼80%) of triazole-resistant A. fumigatus in our sample, the highest reported so far, with a significant proportion of these strains resistant to both tested agricultural fungicides and medical triazole drugs. In addition, we found novel allelic and genotypic diversities and evidence for multiple independent origins of azole-resistant genotypes of A. fumigatus in greenhouse populations in this region. Our study calls for a systematic evaluation of the effects of azole fungicide usage in greenhouses on human health.

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Section: Resultssupporting

confidence: 52%

“…So far, both clinical and environmental samples of ARAF have been found from Europe, America, Africa, New Zealand, the Middle East, and Asia (27,(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Traditionally, the emergence of azole resistance in A. fumigatus populations was believed due to longterm clinical azole therapy.…”

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confidence: 99%

Extensive Genetic Diversity and Widespread Azole Resistance in Greenhouse Populations of Aspergillus fumigatus in Yunnan, China

Zhou

Korfanty

et al. 2021

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“…Since the first reported ITZ-resistant A. fumigatus isolate in 1997, 64 the isolates of azole-resistant A. fumigatus have been increasingly reported worldwide. 7,65,66 The amount of azole fungicide used in China is much higher than those used in European countries, 26 which suggests a high selective pressure for environmental A. fumigatus. Several studies have indicated that the TR 34 /L98H and TR 34 /L98H/S297T/F495I mutations were the predominant mutations in China.…”

Section: Discussionmentioning

confidence: 99%

Aspergillus Species in Lower Respiratory Tract of Hospitalized Patients from Shanghai, China: Species Diversity and Emerging Azole Resistance

Xu¹,

Chen²,

Zhu³

et al. 2020

IDR

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“…Some environments supporting the growth, sexual reproduction, genetic variation and containing residues of azole fungicides could cause these complex mutations to emerge, amplify and spread. So, AR Af may very well emerge in specific environments and spread to other countries due to natural factors such as wind, or anthropogenic factors such as human travel and commercial trade [ 11 , 23 ]. This gene flow could explain the fact that genotypically close AR Af , or those having the same genotype, were found in different countries [ 18 , 19 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…This is compatible with selective gene sweeps accompanying the selection of beneficial mutations and the genetic adaptation of A. fumigatus which enable it to survive and reproduce in prevailing or new environments, such as those with azole fungicides [ 24 , 25 ]. Selective sweeps would reduce allelic diversity and one, or a limited number, of clones would predominate locally [ 23 ]. The lower allelic and STR Af genotype diversity reported for AR Af isolates from sawmills in our study make this hypothesis likely.…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology of Azole-Resistant Aspergillus fumigatus in Sawmills of Eastern France by Microsatellite Genotyping

Jeanvoine

Godeau

Laboissière

et al. 2020

JoF

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Background: Wood chipping has been described as a potential hotspot for the selection of azole-resistant Aspergillus fumigatus (ARAf). We previously reported ARAf isolates in sawmills (Eastern France), most of which contained the TR34/L98H mutation. Methods: To study genotypic relatedness, microsatellite genotyping (short tandem repeat for A. fumigatus (STRAf)) was performed on 41 azole-susceptible A. fumigatus (ASAf) and 23 ARAf isolated from 18 sawmills and two clinical A. fumigatus (sensitive and resistant) isolated from a sinus sample of a woodworker. Results: Fifty-four unique multilocus genotypes (MLGs) were described among the 66 isolates: 13/24 ARAf and 41/42 ASAf. Allelic diversity was higher for ASAf than for ARAf. Among the 24 ARAf, five isolates had their own MLGs. Thirteen ARAf (54%) belonged to the same group, composed of four close MLGs, defined using Bruvo’s distance. Thirty-two of the 42 ASAf (76%) had their own MLGs and could not be grouped with the Bruvo’s distance cutoff used (0.2). Conclusion: Thus, at a regional scale and in the particular environment of the wood industry, common but also different distinct genotypes, even in the same sawmill, were identified. This suggests that the hypothesis of ARAf clonal expansion from a common strain is probably insufficient to explain genotype emergence and distribution.

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Contemporary Gene Flow is a Major Force Shaping the Aspergillus fumigatus Population in Auckland, New Zealand

Cited by 16 publications

References 49 publications

Extensive Genetic Diversity and Widespread Azole Resistance in Greenhouse Populations of Aspergillus fumigatus in Yunnan, China

Extensive Genetic Diversity and Widespread Azole Resistance in Greenhouse Populations of Aspergillus fumigatus in Yunnan, China

Aspergillus Species in Lower Respiratory Tract of Hospitalized Patients from Shanghai, China: Species Diversity and Emerging Azole Resistance

Molecular Epidemiology of Azole-Resistant Aspergillus fumigatus in Sawmills of Eastern France by Microsatellite Genotyping

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