Abstract
Phytophthora nicotianae is a plant-pathogenic oomycete, posing a serious threat to global agriculture due to its highly destructive infections and challenges in management. To explore a biologically based disease management strategy, we investigated Streptomyces ardesiacus HL-06, which produces phenazine-1-carboxamide (PCN), a potent anti-oomycete metabolite that effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions, surpassing the efficacy of commercial fungicides. Mechanistically, we identified CDC48, a AAA+ ATPase essential for mitochondrial homeostasis, as the direct molecular target of PCN. Drug affinity responsive target stability (DARTS), molecular docking, and isothermal titration calorimetry revealed that PCN binds to CDC48's ATPase domain, thereby disrupting mitochondrial protein quality control. This interaction leads to mitochondrial cristae loss, ATP synthase inhibition, and reactive oxygen species (ROS) accumulation, ultimately triggering oomycete apoptosis. This is the first report of a phenazine compound targeting a eukaryotic AAA+ ATPase, revealing a novel mode of action against oomycete pathogens. Our findings integrate microbial ecology with chemical biology, positioning PCN as a promising eco-friendly candidate for sustainable plant disease management.
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Claims 7
Claim · model-written summary
PCN suppresses the in vitro growth of P. nicotianae
- Taxon
- tobacco
Nicotiana tabacume1 - Treatment
- phenazine-1-carboxamide (PCN)e0
- Interactor
- P. nicotianae
Phytophthora nicotianaee1pathogen - Outcome
- growth of P. nicotianae in vitroe1
- Direction
- suppressese1
- Setting
- in vitroe1
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“Streptomyces ardesiacus HL-06, which produces phenazine-1-carboxamide (PCN)”
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
Claim · model-written summary
PCN reduces tobacco black shank severity by over 80% under field conditions
- Taxon
- tobaccoNicotiana tabacume1
- Treatment
- phenazine-1-carboxamide (PCN)e0
- Interactor
- P. nicotianaePhytophthora nicotianaee1pathogen
- Outcome
- black shank severitye1
- Direction
- reducese1
- Value
- over 80%e1
- Setting
- under field conditionse1
Not reportedComparator
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“Streptomyces ardesiacus HL-06, which produces phenazine-1-carboxamide (PCN)”
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
Claim · model-written summary
PCN efficacy surpasses that of commercial fungicides against tobacco black shank
- Taxon
- tobaccoNicotiana tabacume1
- Treatment
- phenazine-1-carboxamide (PCN)e0
- Outcome
- efficacye2
- Direction
- surpassinge2
- Comparator
- commercial fungicidese2
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e0“Streptomyces ardesiacus HL-06, which produces phenazine-1-carboxamide (PCN)”
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
e2“surpassing the efficacy of commercial fungicides”
Claim · model-written summary
PCN binds to the ATPase domain of CDC48
- Taxon
- tobaccoNicotiana tabacume1
- Gene
- CDC48e5
- Compound
- PCNe5
- Outcome
- binds to CDC48's ATPase domaine5
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
e5“PCN binds to CDC48's ATPase domain, thereby disrupting mitochondrial protein quality control”
Claim · model-written summary
The PCN-CDC48 interaction leads to mitochondrial cristae loss, ATP synthase inhibition and reactive oxygen species (ROS) accumulation
- Taxon
- tobaccoNicotiana tabacume1
- Gene
- CDC48e5
- Compound
- PCNe5
- Outcome
- mitochondrial cristae loss, ATP synthase inhibition, and reactive oxygen species (ROS) accumulatione3
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
e3“This interaction leads to mitochondrial cristae loss, ATP synthase inhibition, and reactive oxygen species (ROS) accumulation”
e5“PCN binds to CDC48's ATPase domain, thereby disrupting mitochondrial protein quality control”
Claim · model-written summary
PCN triggers oomycete apoptosis
- Taxon
- tobaccoNicotiana tabacume1
- Interactor
- oomycetee4pathogen
- Compound
- PCNe5
- Outcome
- oomycete apoptosise4
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
e4“ultimately triggering oomycete apoptosis”
e5“PCN binds to CDC48's ATPase domain, thereby disrupting mitochondrial protein quality control”
Claim · model-written summary
PCN is a promising eco-friendly candidate for sustainable plant disease management
- Taxon
- tobaccoNicotiana tabacume1
- Outcome
- promising eco-friendly candidate for sustainable plant disease managemente6
Organisms pictured · Representative pictures of the matched species, not figures from the paper.
Verbatim
e1“effectively suppresses the growth of P. nicotianae in vitro and reduces tobacco black shank severity by over 80% under field conditions”
e6“positioning PCN as a promising eco-friendly candidate for sustainable plant disease management”