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Aspergillus oxylipin signaling and quorum sensing pathways depend on g protein-coupled receptors.

Affeldt KJ, Brodhagen M, Keller NP - Toxins (Basel) (2012)

Bottom Line: Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation.A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production.The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology and Department of Medical Microbiology and Immunology, 1550 Linden Drive, Madison, WI 53706, USA.

ABSTRACT
Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the fungus. G protein-coupled receptors (GPCR) have been speculated to be involved as they are known oxylipin receptors in mammals, and many putative GPCRs have been identified in the Aspergilli. Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation. A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production. A. flavus encodes two putative GprD homologs, GprC and GprD, and we demonstrate here that they are required to transition to a high-density development state, as well as to respond to spent medium of a high-density culture. The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics.

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Related in: MedlinePlus

A hypothetical model is presented in which at low density, cultures of A. flavus produce low amounts of oxylipins (via Ppo and/or Lox enzymes). GprC/D signaling is not activated, and the culture produces AF and sclerotia, but very few conidia. At high density, more oxylipins are produced until their levels exceed a threshold and are recognized by GprC and GprD. This initiates a developmental shift toward conidiation, while very low amounts of sclerotia and AF are produced.
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toxins-04-00695-f006: A hypothetical model is presented in which at low density, cultures of A. flavus produce low amounts of oxylipins (via Ppo and/or Lox enzymes). GprC/D signaling is not activated, and the culture produces AF and sclerotia, but very few conidia. At high density, more oxylipins are produced until their levels exceed a threshold and are recognized by GprC and GprD. This initiates a developmental shift toward conidiation, while very low amounts of sclerotia and AF are produced.

Mentions: The phenotypes of the gpr mutants recapitulated those observed for several of the A. flavus oxygenase mutants, in particular strains deleted for the sole lipoxygenase gene, loxA and one of the ppo genes, ppoC [16,17]. Loss of either one of these genes similarly locked the fungus into a low density phenotype. Like that of the KD::gprCD mutant, the severity of the phenotype was additive in A. flavus strains depleted for the lox and multiple ppo genes. Considering these data together, we present a hypothetical model for GprC/D perception of endogenous oxylipins (Figure 6). We propose that at high-densities, a QS signal triggers wild type cultures to make very little AF and few sclerotia while conidiating profusely. GprC and GprD could be direct receptors of this signal(s), which could be generated by Lox and/or Ppo enzymes. Without these receptors or the enzymes that produce the signals, the fungus remains in a low-density state. Endogenous oxylipins are likely similar in structure to exogenous, plant derived oxylipins, and thus GprC and GprD could be important for fungal-host interactions.


Aspergillus oxylipin signaling and quorum sensing pathways depend on g protein-coupled receptors.

Affeldt KJ, Brodhagen M, Keller NP - Toxins (Basel) (2012)

A hypothetical model is presented in which at low density, cultures of A. flavus produce low amounts of oxylipins (via Ppo and/or Lox enzymes). GprC/D signaling is not activated, and the culture produces AF and sclerotia, but very few conidia. At high density, more oxylipins are produced until their levels exceed a threshold and are recognized by GprC and GprD. This initiates a developmental shift toward conidiation, while very low amounts of sclerotia and AF are produced.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475224&req=5

toxins-04-00695-f006: A hypothetical model is presented in which at low density, cultures of A. flavus produce low amounts of oxylipins (via Ppo and/or Lox enzymes). GprC/D signaling is not activated, and the culture produces AF and sclerotia, but very few conidia. At high density, more oxylipins are produced until their levels exceed a threshold and are recognized by GprC and GprD. This initiates a developmental shift toward conidiation, while very low amounts of sclerotia and AF are produced.
Mentions: The phenotypes of the gpr mutants recapitulated those observed for several of the A. flavus oxygenase mutants, in particular strains deleted for the sole lipoxygenase gene, loxA and one of the ppo genes, ppoC [16,17]. Loss of either one of these genes similarly locked the fungus into a low density phenotype. Like that of the KD::gprCD mutant, the severity of the phenotype was additive in A. flavus strains depleted for the lox and multiple ppo genes. Considering these data together, we present a hypothetical model for GprC/D perception of endogenous oxylipins (Figure 6). We propose that at high-densities, a QS signal triggers wild type cultures to make very little AF and few sclerotia while conidiating profusely. GprC and GprD could be direct receptors of this signal(s), which could be generated by Lox and/or Ppo enzymes. Without these receptors or the enzymes that produce the signals, the fungus remains in a low-density state. Endogenous oxylipins are likely similar in structure to exogenous, plant derived oxylipins, and thus GprC and GprD could be important for fungal-host interactions.

Bottom Line: Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation.A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production.The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Bacteriology and Department of Medical Microbiology and Immunology, 1550 Linden Drive, Madison, WI 53706, USA.

ABSTRACT
Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the fungus. G protein-coupled receptors (GPCR) have been speculated to be involved as they are known oxylipin receptors in mammals, and many putative GPCRs have been identified in the Aspergilli. Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation. A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production. A. flavus encodes two putative GprD homologs, GprC and GprD, and we demonstrate here that they are required to transition to a high-density development state, as well as to respond to spent medium of a high-density culture. The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics.

Show MeSH
Related in: MedlinePlus