in resistance towards azole drugs (Miyazaki
et al. 2013). Whereas individual mutants do
not show increased sensitivity towards osmotic
stress-inducing or cell wall-damaging drugs,
calcineurin/IRE1 double mutants display
decreased resistance (Miyazaki et al. 2013;
Tanaka et al. 2018).
B. The UPR in Plant Pathogenic Fungi
Plant pathogenic fungi use different strategies
to enable the effective colonization of their host
plants. While necrotrophic fungi induce plant
cell death via secretion of proteinaceous effectors, plant cell wall-degrading enzymes or toxins, biotrophic fungi secrete effectors
to establish compatible host-pathogen interactions. Effector molecules subvert the plant
immune system and redirect metabolic fluxes
for interfering with plant cell death-inducing
pathways and keeping their host alive. Hemibiotrophic fungi typically establish an initial
biotrophic interaction that with increasing
time and disease progression is transformed
to a necrotrophic interaction. UPR signaling
in plant pathogens is connected to the ability
of efficient protein secretion, regulation of
effector genes, generation of reactive oxygen
species (ROS), and resistance to plant defense
compounds. Importantly, studies in the biotrophic corn smut fungus Ustilago maydis
revealed an unexpected connection to regulatory pathways controlling pathogenic development and highlight the adaptation of
conserved cellular pathways for lifestylespecific functions in fungal pathogens.
1. Alternaria brassicicola
Alternaria brassicicola is a filamentous ascomycete and necrotrophic pathogen causing black
spot disease in a wide range of plant species
belonging to the Brassicaceae (Cho 2015;
Guillemette et al. 2014). UPR signaling in A.
brassicicola is controlled by the Hac1-like transcription factor AbHacA, which is crucial for
ER stress resistance and important for growth
and conidiation on complex carbon sources
(potato dextrose medium). This phenotype is
further accompanied by defects in cell wall
construction, formation of aberrant enlarged
and swollen hyphae, and hypersensitivity
towards cell wall disturbing compounds.
AbhacA is crucial for virulence in infection
assays on Arabidopsis thaliana and Brassica
oleracea, and deletion mutants are highly susceptible towards the indolic phytoalexin camalexin, a major plant defense compound of A.
thaliana (Glawischnig 2007) and potent activator of the UPR in A. brassicicola. By contrast,
AbhacA-mediated UPR activity is not required
for conidia germination and efficient appressoria formation. Hence, the increased susceptibility towards plant defense compounds, the
reduced vegetative growth, aberrant cell wall,
and the reduced ability for protein secretion
might be causal for the virulence defects in A.
brassicicola.
2. Botrytis cinerea
The filamentous ascomycete Botrytis cinerea is
the causal agent of grey mold disease and one of
the most widespread plant pathogens, infecting
more than 200 host species. The fungal-derived
generation of ROS by the Nox (NADPH Oxidase) complex is important for cellular differentiation, plant penetration, and sclerotia
formation in B. cinerea (Roca et al. 2012; Segmuller et al. 2008; Siegmund et al. 2013). The
protein disulfide isomerase BcPdi1, which mediates oxidative protein folding in the ER, was
identified as an interactor of the NoxA complex. BcPdi1 deletion mutants are reduced in
virulence on Phaseolus vulgaris and display
largely overlapping phenotypes with mutants
of the NoxA signaling pathway, including
reduced resistance to osmotic and redox stress
and abolished formation of conidial anastomosis tubes (CAT) (Marschall and Tudzynski
2017). Phosphorylation of Ire1, as a key determinant of UPR activity, has been found specifically induced under host mimicking growth
conditions (deproteinized tomato cell wall
medium, TCW), suggesting that the UPR is
activated during the infection process of B.
cinerea (Escobar-Nino et al. 2019). The ER
chaperone Bag1 (Bcl-2 associated athanogene
3 Genetics of the Unfolded Protein Response in Fungi
59
et al. 2013). Whereas individual mutants do
not show increased sensitivity towards osmotic
stress-inducing or cell wall-damaging drugs,
calcineurin/IRE1 double mutants display
decreased resistance (Miyazaki et al. 2013;
Tanaka et al. 2018).
B. The UPR in Plant Pathogenic Fungi
Plant pathogenic fungi use different strategies
to enable the effective colonization of their host
plants. While necrotrophic fungi induce plant
cell death via secretion of proteinaceous effectors, plant cell wall-degrading enzymes or toxins, biotrophic fungi secrete effectors
to establish compatible host-pathogen interactions. Effector molecules subvert the plant
immune system and redirect metabolic fluxes
for interfering with plant cell death-inducing
pathways and keeping their host alive. Hemibiotrophic fungi typically establish an initial
biotrophic interaction that with increasing
time and disease progression is transformed
to a necrotrophic interaction. UPR signaling
in plant pathogens is connected to the ability
of efficient protein secretion, regulation of
effector genes, generation of reactive oxygen
species (ROS), and resistance to plant defense
compounds. Importantly, studies in the biotrophic corn smut fungus Ustilago maydis
revealed an unexpected connection to regulatory pathways controlling pathogenic development and highlight the adaptation of
conserved cellular pathways for lifestylespecific functions in fungal pathogens.
1. Alternaria brassicicola
Alternaria brassicicola is a filamentous ascomycete and necrotrophic pathogen causing black
spot disease in a wide range of plant species
belonging to the Brassicaceae (Cho 2015;
Guillemette et al. 2014). UPR signaling in A.
brassicicola is controlled by the Hac1-like transcription factor AbHacA, which is crucial for
ER stress resistance and important for growth
and conidiation on complex carbon sources
(potato dextrose medium). This phenotype is
further accompanied by defects in cell wall
construction, formation of aberrant enlarged
and swollen hyphae, and hypersensitivity
towards cell wall disturbing compounds.
AbhacA is crucial for virulence in infection
assays on Arabidopsis thaliana and Brassica
oleracea, and deletion mutants are highly susceptible towards the indolic phytoalexin camalexin, a major plant defense compound of A.
thaliana (Glawischnig 2007) and potent activator of the UPR in A. brassicicola. By contrast,
AbhacA-mediated UPR activity is not required
for conidia germination and efficient appressoria formation. Hence, the increased susceptibility towards plant defense compounds, the
reduced vegetative growth, aberrant cell wall,
and the reduced ability for protein secretion
might be causal for the virulence defects in A.
brassicicola.
2. Botrytis cinerea
The filamentous ascomycete Botrytis cinerea is
the causal agent of grey mold disease and one of
the most widespread plant pathogens, infecting
more than 200 host species. The fungal-derived
generation of ROS by the Nox (NADPH Oxidase) complex is important for cellular differentiation, plant penetration, and sclerotia
formation in B. cinerea (Roca et al. 2012; Segmuller et al. 2008; Siegmund et al. 2013). The
protein disulfide isomerase BcPdi1, which mediates oxidative protein folding in the ER, was
identified as an interactor of the NoxA complex. BcPdi1 deletion mutants are reduced in
virulence on Phaseolus vulgaris and display
largely overlapping phenotypes with mutants
of the NoxA signaling pathway, including
reduced resistance to osmotic and redox stress
and abolished formation of conidial anastomosis tubes (CAT) (Marschall and Tudzynski
2017). Phosphorylation of Ire1, as a key determinant of UPR activity, has been found specifically induced under host mimicking growth
conditions (deproteinized tomato cell wall
medium, TCW), suggesting that the UPR is
activated during the infection process of B.
cinerea (Escobar-Nino et al. 2019). The ER
chaperone Bag1 (Bcl-2 associated athanogene
3 Genetics of the Unfolded Protein Response in Fungi
59