Friday, 17 August 2018 17:09

H. pylori Urease has a Noncatalytic Role as an Antioxidant

Written by 
Published in mBiosphere

Helicobacter pylori, the bacterial cause of many stomach ulcers, is able to survive in the acidic environment of the stomach by secreting urease, which converts urea into ammonia and makes the microenvironment around the bacteria less acidic. A new Journal of Bacteriology report demonstrates that H. pylori urease is pulling double duty, and that a noncatalytic activity of the enzyme also contributes to bacterial stress survival. 

 

JBacteriology: Noncatalytic Antioxidant Role for Helicobacter pylori Urease

 

The research team, led by first author Alan Schmalstig and senior author Robert Maier, generated 3 noncatalytic urease alleles in different H. pylori strains that disabled the ability of the enzyme to interact with its nickel cofactor. These mutations meant that normal amounts of urease protein were produced by the bacteria, but that the protein couldn’t break down urea. The authors then tested the mutant strains for their ability to withstand stress.

 

2018.8.17 JB urease 1Equal numbers of H. pylori were exposed 1 h to HOCl under microaerophilic conditions. Surviving cells were plated and counted. Source. 

Noncatalytic urease was able to protect H. pylori from exposure to hypochlorous acid (HOCl) (see figure, right), a reactive oxygen species (ROS) produced by neutrophils and other host cells as part of their defense arsenal. H. pylori has many mechanisms, including catalase production, to counteract the potential damage from these ROS, but the authors hypothesized urease may contribute to ROS defense, in part because it’s the major protein produced by the cell. Indeed, they saw that exposure of a urease deletion mutation (ΔureAB) to hypocholorous acid resulted in nearly 10,000-fold decrease in the number of surviving cells. All of the mutant alleles, despite not having urease activity, were able to rescue cell survival to wild-type levels.

 

The additional, noncatalytic activity of urease may give researchers a clue about some unsolved mysteries surrounding this enzyme. Urease is required for normal levels of H. pylori persistence even in neutral-pH environments that don’t require the breakdown of urea, and urease production is increased in response to oxidative stress. 

 

How does urease protect from ROS without any enzymatic activity? H. pylori catalase defends against reactive oxygen species in part through oxidation of its methionine (Met) amino acid residues, and the research team determined that the Met residues of urease have a similar protective function. Oxidation of urease prevents damage to other, more vital proteins or nucleic acids that might be necessary for cell viability. The researchers further found that urease oxidation could be reversed by treatment with the H. pylori Msr protein. Urease and Msr cycling of oxidation-and-reduction likely allows recycling of ROS-quenching urease. 

 

Homologs of urease and Msr are found in bacteria, fungi and archaea; urease is a well-known virulence factor found in several bacterial pathogens. Protection against ROS may be a conserved function in addition to urea hydrolysis. Future studies will be needed to determine whether this noncatalytic activity of urease is conserved in other microbial species.

 

Cover photo credit

Last modified on Friday, 17 August 2018 17:22
Julie Wolf

Julie Wolf is the ASM Science Communications Specialist. She contributes to the ASM social media and blog network and hosts the Meet the Microbiologist podcast. She also runs workshops at ASM conferences to help scientists improve their own communication skills. Follow Julie on Twitter for more ASM and microbiology highlights at @JulieMarieWolf.

Julie earned her Ph.D. from the University of Minnesota, focusing on medical mycology and infectious disease. Outside of her work at ASM, she maintains a strong commitment to scientific education and teaches molecular biology at the community biolab, Genspace. She lives in beautiful New York City.

TPL_asm2013_ADDITIONAL_INFORMATION

TPL_asm2013_SEARCH

7437:h-pylori-urease-has-a-noncatalytic-role-as-an-antioxidant