Related Experiment Video
Updated: Jun 9, 2025
08:52
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
10.6K
Alpha-1 antitrypsin inhibits pertussis toxin.
Stefanie Lietz1, Anja Sommer1, Lena-Marie Sokolowski1
1Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center, Ulm, Germany.
The Journal of Biological Chemistry
|October 31, 2024
Summary
Alpha-1 antitrypsin (α1AT) inhibits pertussis toxin (PT), the main cause of whooping cough. This discovery offers a potential new treatment for this re-emerging infectious disease.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Pertussis (whooping cough) is a highly infectious respiratory illness caused by Bordetella pertussis.
- It is re-emerging globally, with no effective treatments currently available, posing risks to unvaccinated individuals, especially newborns.
- Pertussis toxin (PT) is a key virulence factor driving disease severity.
Purpose of the Study:
- To identify novel inhibitors of pertussis toxin (PT).
- To investigate the therapeutic potential of alpha-1 antitrypsin (α1AT) as a PT inhibitor for pertussis treatment.
Main Methods:
- Utilized peptide libraries, bioassay-guided fractionation, and mass spectrometry to discover PT inhibitors.
- Conducted in vitro experiments including biochemistry, cell culture, and molecular modeling to elucidate α1AT's mechanism of action.
- Evaluated α1AT efficacy in an infant mouse model of severe pertussis.
Main Results:
- Identified α1AT as a potent inhibitor of PT.
- Demonstrated that α1AT blocks PT binding to host target cells.
- Observed reduced α1AT expression during infection and significant reduction in B. pertussis-induced leukocytosis following systemic α1AT administration in mice.
Conclusions:
- α1AT is a novel inhibitor of pertussis toxin.
- α1AT warrants further development as a potential therapeutic agent for pertussis.
- Existing clinical use of α1AT for deficiency suggests potential for repurposing in pertussis management.
Keywords:
Bordetella pertussisG-proteinbacterial toxinhost defenseinfectious diseaseinhibitorpertussispertussis toxintoxin inhibitorwhooping coughα(1)-antitrypsinMore Related Videos
Related Concept Videos
01:30The Electron Transport Chain
16.2K
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
16.2K
01:09GPCRs Regulate Adenylyl Cylase Activity
5.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.3K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.7K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.7K
01:19Allosteric Proteins-ATCase
5.7K
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...
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...
5.7K
01:26Anticholinesterase Agents: Poisoning and Treatment
796
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
796