Ureases display biological effects independent of enzymatic activity: Is there a connection to diseases caused by urease-producing bacteria?

Abstract

Ureases are enzymes from plants, fungi and bacteria that catalyze the hydrolysis of urea to form ammonia and carbon dioxide. While fungal and plant ureases are homo-oligomers of 90-kDa subunits, bacterial ureases are multimers of two or three subunit complexes. We showed that some isoforms of jack bean urease, canatoxin and the classical urease, bind to glycoconjugates and induce platelet aggregation. Canatoxin also promotes release of histamine from mast cells, insulin from pancreatic cells and neurotransmitters from brain synaptosomes. In vivo it induces rat paw edema and neutrophil chemotaxis. These effects are independent of ureolytic activity and require activation of eicosanoid metabolism and calcium channels. Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach mucosa, causes gastric ulcers and cancer by a mechanism that is not understood. H. pylori produces factors that damage gastric epithelial cells, such as the vacuolating cytotoxin VacA, the cytotoxin-associated protein CagA, and a urease (up to 10% of bacterial protein) that neutralizes the acidic medium permitting its survival in the stomach. H. pylori whole cells or extracts of its water-soluble proteins promote inflammation, activate neutrophils and induce the release of cytokines. In this paper we review data from the literature suggesting that H. pylori urease displays many of the biological activities observed for jack bean ureases and show that bacterial ureases have a secretagogue effect modulated by eicosanoid metabolites through lipoxygenase pathways. These findings could be relevant to the elucidation of the role of urease in the pathogenesis of the gastrointestinal disease caused by H. pylori.

New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis

“…The enzymatic function of urease is to produce ammonia and carbon dioxide from urea. However, recent studies on plant ureases suggest that they play a role in defense mechanisms and have biological function independent of their enzymatic activity (Olivera-Severo et al 2006). The A. baumannii urease gene may play a similar role.…”

Crystal Structure of the First Plant Urease from Jack Bean: 83 Years of Journey from Its First Crystal to Molecular Structure

“…6,15 Both bacterial and plant ureases display several biological activities that are independent of their ureolytic activity. [16][17][18][19][20] For example, enzymatic activity is not involved in platelet aggregation and antifungal activities of plant and microbial ureases. 17,19,20 Similarly, the lethal activity of canatoxin (an isoform of JBU) in mice and the insecticidal activity of plant ureases are independent of ureolytic activity.…”

Functional and Phylogenetic Analysis of ureD in Shiga Toxin-Producing Escherichia coli

“…Urease, a cytoplasmic enzyme, catalyzes the hydrolysis of urea to form ammonia and carbon dioxide, providing both an increase in pH and a readily assimilated source of nitrogen (32). Recent studies have shown that bacterial ureases may encode other biological activities independently of their ureolytic activity, such as induction of platelet aggregation and activation of lipooxygenases (37). The EHEC ure gene cluster, ureDABCEFG, contains the seven genes necessary to form active urease.…”