Mediates attachment to plasmin or plasminogen in another organism

[genegodbold]

For new term requests, please provide the following information:

Preferred term label

Mediates attachment to host plasminogen. See issue #169.

Textual definition

This term covers parasite protein that binds host plasminogen, a serine proteinase zymogen that circulates in the blood (https://en.wikipedia.org/wiki/Plasmin). This plasminogen recruitment can result in the inhibition OR promotion of fibrinolysis in the blood or tissues. It can also result in the inhibition of complement via activated plasmin being recruited to cleave the membrane attack complex or related components.

There are more than two dozen of these for bacteria. It does not look like some weird accident but rather an oft-explored evolutionary strategy for subverting host processes.

Suggested parent term

PATHGO_0000147 Mediates adherence in another organism Why? This doesn't mediate adhesion (PATHGO_0000038), so I'm going with the next higher level term

Attribution

https://orcid.org/0000-0002-5702-4690

[jproesch]

@genegodbold interestingly there is no GO term currently covering binding, but there is one for activation. What is typically the immediate consequence of the binding for the examples you mention? Activation to plasmin then indirect complement inactivation?

[genegodbold]

Yep, the activated plasmin then inactivates complement on the surface of the bacterium. @jproesch

[genegodbold]

Here is an example from Staphylococcus aureus:

Efb is a secreted protein that binds to the complement component C3b and fibrinogen [PMID15243934]. Efb inhibits complement activation and blocks opsonization (and subsequent phagocytosis) in a dose-dependent manner. Efb binds to the alpha-chain of C3 and inhibits both the classical and lectin pathways of complement activation. Efb blocks deposition of C3 on the bacterial surface [PMID15243934]. Efb blocks the formation of the functional C3b opsonin by binding tightly to the thioester-containing domain of the native C3 and by altering its conformation such that it becomes incapable of being processed into C3b [PMID17351618]. Together Sbi and Efb bind complement components C3 and C3b simultaneously with human plasminogen. The bound plasminogen is converted by secreted staphylokinase or by a host-specific urokinase to plasmin which in turn leads to degradation of both C3 and C3b. The bound plasmin also degrades C3a. Sbi and Efb comprise a platform for recruitment of plasminogen, C3 and C3b for efficient degradation of the complement components. Efb enhances the degradation of C3/C3b more than Sbi, probably because it has a higher binding affinity for C3d (Efb dissociation constant for C:Cd3 = 0.3 nanomolar while Sbi = 1.4 micromolar). Plasmin cleaves C3b at several sites and generates C3c and C3d [PMID23071827].

[jproesch]

@genegodbold

"together Sbi and Efb bind complement components C3 and C3b simultaneously with human plasminogen. The bound plasminogen is converted by secreted staphylokinase or by a host-specific urokinase to plasmin which in turn leads to degradation of both C3 and C3b. The bound plasmin also degrades C3a. Sbi and Efb comprise a platform for recruitment of plasminogen, C3 and C3b for efficient degradation of the complement components."

So in this case plasminogen/plasmin is being recruited to degrade complement? This fits pretty squarely under "indirect host complement activation"...

[jproesch]

@genegodbold I see I had a similar inclination here...to try to fit this in with indirect complement inactivation