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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

Amino acid sequences for A. nidulans GprD and A. flavus GprC and GprD were aligned using Clustal Omega [55,56] and Jalview [57,58] with Blosum62 coloring scheme. According to this scheme, gaps are colored white, matching residues are colored dark blue, and non-matching but positively scored residues are colored light blue.
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toxins-04-00695-f008: Amino acid sequences for A. nidulans GprD and A. flavus GprC and GprD were aligned using Clustal Omega [55,56] and Jalview [57,58] with Blosum62 coloring scheme. According to this scheme, gaps are colored white, matching residues are colored dark blue, and non-matching but positively scored residues are colored light blue.

Mentions: Because of the growth and sporulation defects of the A. nidulans ∆gprD strain [50] and it not being a pathogen of note, we followed up with physiology studies with mutants of the homologous gprD genes in the agriculturally relevant species, A. flavus. As A. nidulans is a model organism for other filamentous fungi, including A. flavus, we reasoned that if GprD was involved in oxylipin perception, then it could play a role in A. flavus biology, as A. flavus oxylipin mutants are aberrant in spore and sclerotial development [16,17]. A. nidulans encodes at least sixteen putative GPCRs [38]. BLAST searches querying each of these GPCRs identified fifteen putative GPCRs in A. flavus. Of these, two appear to be highly similar to A. nidulans GprD. The first of these is A. flavus GprD (AFLA_135680), which shares 67% amino acid identity (e-value 2e-164) with A. nidulans GprD. The second we call GprC (AFLA_074150), and it shares 47% identity (e-value 6e-87) with A. nidulans GprD and 47% identity with A. flavus GprD (e-value 1e-119). An alignment of all three GPCRs is provided in Figure S2.


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

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

Amino acid sequences for A. nidulans GprD and A. flavus GprC and GprD were aligned using Clustal Omega [55,56] and Jalview [57,58] with Blosum62 coloring scheme. According to this scheme, gaps are colored white, matching residues are colored dark blue, and non-matching but positively scored residues are colored light blue.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

toxins-04-00695-f008: Amino acid sequences for A. nidulans GprD and A. flavus GprC and GprD were aligned using Clustal Omega [55,56] and Jalview [57,58] with Blosum62 coloring scheme. According to this scheme, gaps are colored white, matching residues are colored dark blue, and non-matching but positively scored residues are colored light blue.
Mentions: Because of the growth and sporulation defects of the A. nidulans ∆gprD strain [50] and it not being a pathogen of note, we followed up with physiology studies with mutants of the homologous gprD genes in the agriculturally relevant species, A. flavus. As A. nidulans is a model organism for other filamentous fungi, including A. flavus, we reasoned that if GprD was involved in oxylipin perception, then it could play a role in A. flavus biology, as A. flavus oxylipin mutants are aberrant in spore and sclerotial development [16,17]. A. nidulans encodes at least sixteen putative GPCRs [38]. BLAST searches querying each of these GPCRs identified fifteen putative GPCRs in A. flavus. Of these, two appear to be highly similar to A. nidulans GprD. The first of these is A. flavus GprD (AFLA_135680), which shares 67% amino acid identity (e-value 2e-164) with A. nidulans GprD. The second we call GprC (AFLA_074150), and it shares 47% identity (e-value 6e-87) with A. nidulans GprD and 47% identity with A. flavus GprD (e-value 1e-119). An alignment of all three GPCRs is provided in Figure S2.

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