Secret garden: Drug-resistant pathogen strains meet and evolve on plant bulbs

In a study published in August in Environmental Microbiology researchers from the University of Tsukuba and Chiba University have revealed that plant bulbs harboring a potentially lethal pathogen also make the perfect lab for evolving fungicide-resistant strains.

The risk associated with fungal infections is increasing, with occurrences of pulmonary aspergillosis (PA), a deadly fungal infection caused by the human pathogen Aspergillus fumigatus, rising globally. Of particular concern are influenza-related PA and COVID-19-related PA, the case numbers of which are growing quickly. Azoles -- a class of antifungal compounds often used as antifungal drugs to treat aspergillosis -- are also widely used as agricultural fungicides. Azole-resistant strains of A. fumigatus are spreading in the environment, potentially promoted by agricultural azole use. Azole resistance is a factor known to affect the treatment of PA, and there is concern that this problem is only worsening.

"Understanding how the genetic variation linked with azole resistance in A. fumigatus strains is distributed and enriched in the environment is necessary for suppressing resistant strains," says senior author of the study Daisuke Hagiwara. "In this study, we set out to do this by investigating the genetics of those strains."

Previously, the research team found several azole-resistant A. fumigatus strains attached to imported plant bulbs for sale in Japanese gardening shops. In this study, they investigated eight strains of azole-resistant A. fumigatus isolated from a single tulip bulb bought in Japan. The researchers used genome sequencing and comparative analysis, and compared the strains for sensitivity to agricultural and medical azoles, in addition to other classes of fungicides. The results indicated that there had previously been genetic recombination between the strains, and that some of them exhibited tolerance to other fungicide classes.

"Our results show that plant bulbs provide not just a vehicle for this pathogen, but also an ideal niche for its strains to encounter each other, and to evolve their resistance to drugs," says Hagiwara.

This study fills gaps in the knowledge of azole-resistant A. fumigatus, providing important information on the genetics behind an urgent global One Health challenge. The research team's findings will inform a deeper understanding of drug-resistant fungi and help with the development of future solutions to this problem.

This study was supported by a grant from the Institute for Fermentation, Osaka (to DH). HT was partly supported by the National Bioscience Database Center (NBDC) of the Japan Science and Technology Agency (JST), and JSPS KAKENHI Grant Numbers 21K07001 and 16H06279. DH and HT were partly supported by AMED, Grant Number JP19fm0208024.