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Aureolysin is an extracellular metalloprotease expressed by Staphylococcus aureus. This protease is a major contributor to the bacterium's virulence, or ability to cause disease, by cleaving host factors of the innate immune system as well as regulating S. aureus secreted toxins and cell wall proteins. To catalyze its enzymatic activities, aureolysin requires zinc and calcium which it obtains from the extracellular environment within the host.

Genetics
Aureolysin is encoded by the gene aur which is located on a monocistronic operon. The gene exists in two allelic forms but the sequence is highly conserved with 89% homology between the two. The gene contains a coding sequence of 1,527 nucleotides that translates into a pre-pro-form of the enzyme that is 509 amino acids long. Of the 509 amino acids, only 301 denote the mature form of aureolysin. After translation, the pre-portion of the enzyme is a 27 amino acid N-terminal signal peptide that acts as a guide to the secretion system located within the cell wall. Here, the signal peptide is cleaved upon secretion of aureolysin.

Aureolysin is largely co-expressed with other major proteases of S. aureus including the two cystine proteases, Staphopain A (ScpA) and B (SspB), and a serine protease V8 (SspA). The transcriptional regulation of aur is controlled by "housekeeping" sigma factor σA and is up-regulated by the accessory gene regulator, agr. Transcription is repressed by staphylococcal accessory regulator sarA and by alternative sigma factor σB. Expression of aur is highly expressed in post-exponential growth phase however, up-regulation of aureolysin during phagocytosis have also been observed.

Activation
Aureolysin, along with V8, SspB, and ScpA, are all secreted a zymogens. This means that they are secreted in an inactive conformation until the propeptide is removed in some manner. Aureolysin, V8, and SspB constitute what is known as the staphylococcal proteolytic cascade. All three of these proteases are secreted into the environment with the propeptide inhibiting their activation. Aureolysin undergoes autocatalysis and the propeptide is degraded generating the mature form of the enzyme. Mature aureolysin will then cleave the propeptide from V8, causing this protease to become active. Finally V8 will cleave SspB propeptide and the cascade is now complete. ScpA becomes mature by autocatalytic degradation of the propeptide, similar to that of aureolysin.

The acive residues of aureolysin are of critical importance to its enzymatic function. The active residue is a glutamate amino acid located at the 145th position of the protein.

Function
Inhibition of the complement system is a major role of aureolysin.

Aureolysin cleaves different proteins among inflammatory regulators and immune components. Aureolysin can inactivate certain targets within the complement system, inhibiting all three pathways of complement activation. Aureolysin cleaves and inactivates protease inhibitor α1-antichymotrypsin and partially inactivate α1-antitrypsin, de-regulating endogenous proteolytic activity. The cleavage of α1-antitrypsin generates a fragment chemotactic to neutrophils. Aureolysin has also been shown to cleave the antimicrobial peptide LL-37.

Aureolysin proteolytically activate pro-thrombin into thrombin, but somewhat contradictory also activates urokinase, and inactivates α2-antiplasmin and plasminogen activator inhibitor-1. It could potentially contribute to either coagulation triggered by coagulase or to fibrinolysis mediated by staphylokinase, or both.

Aureolysin can cleave a bacterial surface proteins, including clumping factor B, and secreted proteins, i.a. phenol-soluble modulins (PSMs) and α-toxins