Wide distribution of resistance to the fungicides fludioxonil and iprodione in Penicillium species

PLoS One. 2022 Jan 31;17(1):e0262521. doi: 10.1371/journal.pone.0262521. eCollection 2022.


Fludioxonil and iprodione are effective fungicides widely used for crop protection and are essential for controlling plant pathogenic fungi. The emergence of fungicide-resistant strains of targeted pathogens is regularly monitored, and several cases have been reported. Non-targeted fungi may also be exposed to the fungicide residues in agricultural fields. However, there are no comprehensive reports on fungicide-resistant strains of non-targeted fungi. Here, we surveyed 99 strains, representing 12 Penicillium species, that were isolated from a variety of environments, including foods, dead bodies, and clinical samples. Among the Penicillium strains, including non-pathogenic P. chrysogenum and P. camembertii, as well as postharvest pathogens P. expansum and P. digitatum, 14 and 20 showed resistance to fludioxonil and iprodione, respectively, and 6 showed multi-drug resistance to the fungicides. Sequence analyses revealed that some strains of P. chrysogenum and Penicillium oxalicum had mutations in NikA, a group III histidine kinase of the high-osmolarity glycerol pathway, which is the mode of action for fludioxonil and iprodione. The single nucleotide polymorphisms of G693D and T1318P in P. chrysogenum and T960S in P. oxalicum were only present in the fludioxonil- or iprodione-resistant strains. These strains also exhibited resistance to pyrrolnitrin, which is the lead compound in fludioxonil and is naturally produced by some Pseudomonas species. This study demonstrated that non-targeted Penicillium strains distributed throughout the environment possess fungicide resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Cadaver
  • Crops, Agricultural / microbiology
  • Dioxoles / pharmacology*
  • Drug Resistance, Fungal*
  • Food Analysis
  • Fungal Proteins / genetics*
  • Fungicides, Industrial / pharmacology
  • Humans
  • Hydantoins / pharmacology*
  • Mycoses / drug therapy*
  • Mycoses / genetics
  • Mycoses / microbiology
  • Penicillium / drug effects
  • Penicillium / genetics
  • Penicillium / isolation & purification*
  • Polymorphism, Single Nucleotide*
  • Pyrroles / pharmacology*


  • Dioxoles
  • Fungal Proteins
  • Fungicides, Industrial
  • Hydantoins
  • Pyrroles
  • Aminoimidazole Carboxamide
  • fludioxonil
  • iprodione

Grants and funding

This study was supported by a grant from the Institute for Fermentation, Osaka and partly by the National Bioresource Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.