Related Experiment Video

Updated: Nov 30, 2025

Expression, Purification, Crystallization, and Enzyme Assays of Fumarylacetoacetate Hydrolase Domain-Containing Proteins
10:21

Expression, Purification, Crystallization, and Enzyme Assays of Fumarylacetoacetate Hydrolase Domain-Containing Proteins

Published on: June 20, 2019

24.7K

Deacidification by FhlA-dependent hydrogenase is involved in urease activity and urinary stone formation in

Wen-Yuan Lin1, Shwu-Jen Liaw2,3

  • 1Department and Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, No. 1, Chang-Te Street, Taipei, 10016, Taiwan, ROC.

Scientific Reports
|November 12, 2020
PubMed

Insights

Proteus mirabilis uses formate hydrogenlyase (FHL) to deacidify the medium, boosting urease activity, urinary stone formation, and colonization. Targeting FHL offers a strategy against urinary tract infections.

Area of Science:

  • Microbiology
  • Urology
  • Biochemistry

Background:

  • Proteus mirabilis is a key uropathogen causing urinary stone formation.
  • Formate hydrogenlyase (FHL) is implicated in P. mirabilis virulence.
  • The FHL system comprises formate dehydrogenase H and hydrogenase, crucial for proton-to-hydrogen conversion.

Purpose of the Study:

  • To investigate the roles of P. mirabilis FHL hydrogenase and its activator, FhlA, in virulence.
  • To understand the contribution of FHL-mediated deacidification to urease activity and stone formation.
  • To assess the impact of FHL system mutations on P. mirabilis colonization in a murine model.

Main Methods:

  • Generating fhlA and hyfG mutants in P. mirabilis.
  • Assessing acid resistance and medium deacidification capabilities of mutant strains.
  • Measuring urease activity across a pH range (5-9).
  • Evaluating urinary stone formation in synthetic urine.
  • Determining bacterial colonization levels in mice.

Main Results:

  • fhlA and hyfG mutants showed defects in acid resistance and delayed medium deacidification.
  • Loss of fhlA or hyfG reduced urease activity between pH 5-8.
  • Mutations in fhlA or hyfG decreased urinary stone formation.
  • fhlA and hyfG mutants exhibited attenuated colonization in mice.

Conclusions:

  • FHL system expression (fhlA and hyf) facilitates medium deacidification by enhancing urease activity.
  • This deacidification process is critical for urinary stone formation and P. mirabilis colonization.
  • The link between acid resistance and urease activity presents a potential therapeutic target for P. mirabilis UTIs.

More Related Videos

An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection07:57

An In Vitro Bladder Model of Catheter-Associated Urinary Tract Infection

Published on: June 24, 2025

788
Detection of the pH-dependent Activity of Escherichia coli Chaperone HdeB In Vitro and In Vivo08:32

Detection of the pH-dependent Activity of Escherichia coli Chaperone HdeB In Vitro and In Vivo

Published on: October 23, 2016

10.9K

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.7K
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
949
Urinary Tract Infection II: Pathophysiology01:25

Urinary Tract Infection II: Pathophysiology

The pathophysiology of urinary tract infections (UTIs) encompasses several progressive stages, beginning with bacterial colonization and culminating in potential systemic complications if untreated. UTIs are primarily initiated by bacteria, such as Escherichia coli, which often originate from the gastrointestinal tract and migrate to the urinary system through the periurethral area. This migration can occur via several routes, including improper hygiene practices, sexual activity, or...
345
Pathophysiology of Peptic Ulcer Disease: Injurious Factors01:22

Pathophysiology of Peptic Ulcer Disease: Injurious Factors

Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
917
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.2K
Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors01:13

Acid Suppressive Drugs for Peptic Ulcer Disease: Proton Pump Inhibitors

Peptic ulcers, often induced by H. pylori infections or NSAID usage, arise from disruptions in the delicate balance of gastric acid production. Peptic ulcers stem from heightened gastric acid levels due to H. pylori infections or NSAID use. The protective mucus layer diminishes in the presence of these factors, allowing gastric acid to erode the stomach lining and form ulcers.
Gastric acid, a potent cocktail of hydrogen and chloride ions, is produced in specialized parietal cells within the...
687