Add references for GO:0043963 perturbation of host adenylate cyclase-mediated signal transduction

[pgaudet]

GO:0043963 perturbation of host adenylate cyclase-mediated signal transduction GO:0043965 symbiont-mediated suppression of host adenylate cyclase-mediated signal transduction

No annotations, no reference.

Might correspond to PATHGO:0000174 regulates host cell adenylate cyclases/phosphodiesterases in another organism ??

[pgaudet]

@genegodbold Do you have references for these?

[genegodbold]

So these things perturb host adenylate cyclase signal transduction because they themselves are adenylate cyclases and they flood host cells with cAMP.

• Edema factor from Bacillus anthracis (P40136): Edema factor is a calmodulin-dependent adenylate cyclase that can convert up to 2000 adenosine triphosphate (ATP) molecules to cyclic AMP (cAMP) per second [PMID:26978402]. The accumulation of cAMP blocks production of tumor necrosis factor (TNF) in monocytes, thereby impairing their bactericidal activity [PMID:15558214]. Mutational studies indicate that the presence of EF is sufficient enough to suppress the chemokine IL-8. It also interferes with transcription and secretion of neutrophil chemokines, as well as neutrophil recruitment during active infection [PMID:18698416].
• Adenylate cyclase toxin (ACT) from Bordetella pertussis (P0DKX7; J7QLC0; Q57506): ACT causes upregulation and accumulation of cAMP in host T cells, which triggers PKA activation. PKA then inhibits T-cell activation by blocking the host MAP kinase cascade, which then interferes with chemokine receptor signaling and inhibits T-cell chemotaxis [PMID:18426886]. The absence of the genes for adenylate cyclase toxin and hemolysin in B. pertussis results in a decrease in median lethal dose for the organism in an infant mouse model from 2000 organisms (per mouse) to 30 million organisms [PMID:2872097]. The adenylate cyclase toxin is enhanced by the Ca2+-binding protein calmodulin. The AC toxin's primary function appears to be the dysregulation and paralysis of host phagocytic cells. This activity is thought to prolong the persistence of the bacteria in the host [PMID:16390441].
• Pseudomonas exotoxin Y (ExoY) (A0A2V2TH22): ExoY is an adenylate cyclase of Pseudomonas aeruginosa that is injected into host cells via a type 3 secretion system (T3SS). ExoY induces epithelial cell rounding that is associated with the disruption of the actin cytoskeleton. This disruption is preceded by actin redistribution to the margins of the cell. ExoY promotes cAMP accumulation in vascular endothelial cells and increases vascular permeability [PMID:16039071]. ExoY modulates host inflammasome activity resulting in a delay of caspase-1 and NFkappaB activation [PMID:28815941]. ExoY activity is enhanced by host filamentous actin [PMID29258848]. When used to infect pulmonary microvascular endothelial cells, a mutant P. aeruginosa that could only inject the ExoY protein (and no others) elevated cAMP levels by 800 fold within four hours. This cAMP was localized to a cytosolic microdomain and induced endothelial gap formation, thereby disrupting the barrier function of the endothelium [PMID:15192021]. In a mouse model of acute lung infection ExoY targets the integrity of the lung epithelium thereby facilitating the penetration of bacteria into the parenchyma [PMID:29734720].

[pgaudet]

Hi @genegodbold

This seems to be covered by another term, GO:0141042 symbiont-mediated cAMP intoxication of host cell; maybe we obsolete the other 2 terms above, GO:0043963 perturbation of host adenylate cyclase-mediated signal transduction and GO:0043965 symbiont-mediated suppression of host adenylate cyclase-mediated signal transduction?

[pgaudet]

Propose to obsolete: after looking at the annotations by PathGO, and in PubMed, we dont have examples of this.

Consider: GO:0141042 symbiont-mediated cAMP intoxication of host cell or GO:0075118 'perturbation of host G protein-coupled receptor signal transduction pathway'

[pgaudet]

Dear all,

The proposal has been made to obsolete GO:0043963 perturbation of host adenylate cyclase-mediated signal transduction GO:0043965 symbiont-mediated suppression of host adenylate cyclase-mediated signal transduction

The reason for obsoletion is that these terms are redundant with other existing terms: GO:0141042 symbiont-mediated cAMP intoxication of host cell and GO:0075118 'perturbation of host G protein-coupled receptor signal transduction pathway'

There are no annotations to these terms, these terms are not present in any subsets.

You can comment on the ticket: https://github.com/geneontology/go-ontology/issues/26165

Thanks, Pascale

[genegodbold]

@pgaudet, the examples of the adenylate cyclases from pathogens given above would be, maybe, cAMP intoxication via adenylate cyclase in another organism? That doesn't sound right, though.