Urease Activity in Anaerobic Gram-Positive Bacteria from the Human Large Intestine

Abstract

The human gastrointestinal tract consists of several discrete compartments including the stomach, small intestine, and large intestine or colon.  Each of these structures has its own microenvironment and microbiota and can contribute in different ways to normal nitrogen metabolism.  One important metabolite in the large intestine is urea, which is formed as a result of amino acid catabolism.  This urea can be degraded by bacteria possessing the enzyme urease (urea amidohydrolase, EC 3.5.1.5).  This review indicates that isolates of several intestinal anaerobic Gram-positive genera including Clostridium, Paenclostridium, Bifidobacterium, and Blautia are urease-positive.  The enzymes have not been characterized biochemically in detail but some appear to be inducible by urea.  Genomic analysis suggests that the ureases from Clostridium, Paenclostridium, and Blautia are composed of the same three types of subunits found in other bacteria.  However, the enzyme from Bifidobacterium may be more similar to that of Helicobacter pylori in that it consists of only two subunits. Physiological studies indicate that many gastrointestinal diseases including hyperammonemia, irritable bowel syndrome, ulcerative colitis, and Crohn’s disease are associated with changes in the gut microbiome.  There is often a decrease in Gram-positive bacteria (Firmicutes) such as Clostridium and an increase in Gram-negative bacteria (Proteobacteria) such as Escherichia coli, but changes in urease-positive species have not systematically been studied.  Attempts to treat these diseases with chemicals that inhibit urease activity or to alter the intestinal microbiome by fecal microbiota transplantation have yielded mixed results.  There is still much research to be done on the intestinal anaerobic Gram-positive bacteria and their contributions to human health and disease.  Future studies should focus on the biochemistry of the ureases from these bacteria including their native and subunit structures, their modes for regulation, and their potential for inhibtion, as well as the specific contributions of these microorganisms to gastrointestinal disorders.