Aldo‐keto reductase from Helicobacter pylori– role in adaptation to growth at acid pH

Abstract

Pyridine‐linked oxidoreductase enzymes of Helicobacter pylori have been implicated in the pathogenesis of gastric disease. Previous studies in this laboratory examined a cinnamyl alcohol dehydrogenase that was capable of detoxifying a range of aromatic aldehydes. In the present work, we have extended these studies to identify and characterize an aldoketo reductase (AKR) enzyme present in H. pylori. The gene encoding this AKR was identified in the sequenced strain of H. pylori, 26695. The gene, referred to as HpAKR, was cloned and expressed in Escherichia coli as a His‐tag fusion protein, and purified using nickel chelate chromatography. The gene product (HpAKR) has been assigned to the AKR13C1 family, although it differs in specificity from the two other known members of this family. The enzyme is a monomer with a molecular mass of approximately 39 kDa on SDS/PAGE. It reduces a range of aromatic aldehyde substrates with high catalytic efficiency, and exhibits dual cofactor specificity for both NADPH and NADH. HpAKR can function over a broad pH range (pH 4–9), and has a pH optimum of 5.5. It is inhibited by sodium valproate. Its substrate specificity complements that of the cinnamyl alcohol dehydrogenase activity in H. pylori, giving the organism the capacity to reduce a wide range of aldehydes. Generation of an HpAKR isogenic mutant of H. pylori demonstrated that HpAKR is required for growth under acidic conditions, suggesting an important role for this enzyme in adaptation to growth in the gastric mucosa. This AKR is a member of a hitherto little‐studied class.

YqhD: a broad-substrate range aldehyde reductase with various applications in production of biorenewable fuels and chemicals

“…Pending an exhaustive search such as that performed by (Villiers and Hollfelder 2009), it is difficult to compare YqhD's substrate promiscuity to TycA. Other aldo-keto reductases with a broad range of substrate specificity have been identified, including AKR from Helicobacter pylori and YvgN and YtbE from Bacillus subtilis, though these enzymes show a preference for nitrobenzaldehydes, chlorobenzaldehydes and pyridine aldehydes in contrast to the relatively simple aldehydes reported to be utilized by YqhD (Cornally et al 2008;Lei et al 2009). …”

Ulcerogenic Helicobacter pylori Strains Isolated from Children: A Contribution to Get Insight into the Virulence of the Bacteria

“…It was described as an essential enzyme for growth at acidic pH [39], and is involved in the removal of toxic aldehydes and ketones of the cell. Again, the abundance of this protein in the proteome of the GU-associated strain 499/02 was equivalent to that in NUD strains, further corroborating the idea that only the DU-associated pediatric H. pylori strains are prepared to face a hyper-acidic environment.…”

Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases

“…Moreover, H. pylori is able to tolerate a broad range of oxygen concentrations (Bury-Mone et al 2006) and H. pylori possesses a plethora of enzyme activities that enables for survival at low pH in the stomach that may be also important during H. pylori -based skin infection, e.g. urease that converts urea to ammonium and carbon dioxide leading to local alkalization of acid pH in the stomach (Bury-Mone et al 2001; Cornally et al 2008; Tuzun et al 2010). Thus, H. pylori is able to survive outside the gastrointestinal tract and its presence in other human tissues may affect host physiology and potentially provoke extragastric disorders.…”