Related Experiment Video
Updated: Jun 3, 2026
12:23
Recombinant Protein Expression, Crystallization, and Biophysical Studies of a Bacillus-conserved Nucleotide Pyrophosphorylase, BcMazG
Published on: May 16, 2017
Secreted Bacillus anthracis proteases target the host fibrinolytic system
Myung-Chul Chung1, Shelley C Jorgensen, Jessica H Tonry
1National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA, USA. mchung3@gmu.edu
FEMS Immunology and Medical Microbiology
|March 15, 2011
Summary
Bacillus anthracis proteases NprB and InhA target the host fibrinolytic system. NprB activates pro-urokinase plasminogen activator, while InhA degrades thrombin-activatable fibrinolysis inhibitor, impacting anthrax pathogenesis.
Area of Science:
- Microbiology
- Biochemistry
- Pathogenesis
Background:
- Pathogenic bacteria frequently target the host fibrinolytic system, promoting bacterial spread and inflammation.
- Bacillus anthracis proteases are potential mediators of host-pathogen interactions.
Purpose of the Study:
- To investigate the roles of Bacillus anthracis secreted proteases NprB and InhA in activating the host fibrinolytic system.
- To determine the specific targets of NprB and InhA within the fibrinolytic cascade.
Main Methods:
- In vitro assays were used to assess the activation of human pro-urokinase plasminogen activator (pro-uPA) by NprB and InhA.
- Degradation of thrombin-activatable fibrinolysis inhibitor (TAFI) by InhA was evaluated in vitro.
- TAFI levels were measured in mice infected with B. anthracis and isogenic inhA deletion mutants.
Main Results:
- NprB efficiently activated pro-uPA and targeted plasminogen activator inhibitors (PAI)-1, 2, and the uPA receptor in vitro.
- InhA demonstrated potent in vitro degradation of TAFI.
- Mice infected with B. anthracis exhibited decreased blood TAFI levels, which were restored in animals infected with inhA deletion mutants.
Conclusions:
- NprB and InhA secreted by Bacillus anthracis contribute to the activation of the host fibrinolytic system.
- These proteases may play significant roles in the pathogenesis of anthrax by modulating fibrinolysis and TAFI levels.
Related Concept Videos
01:25Inhalation Anthrax
Anthrax is a zoonotic disease caused by Bacillus anthracis, a Gram-positive, spore-forming bacterium. It primarily affects herbivorous animals but can be transmitted to humans through skin contact, ingestion, or inhalation of spores.Cutaneous anthrax, the most common form, typically results from direct contact with bacterial spores through skin abrasions and is generally less severe. Gastrointestinal anthrax results from eating undercooked or contaminated meat. It affects the mouth, throat, or...
01:20Determinants of Bacterial Pathogenicity and Virulence
Pathogenic bacteria employ a variety of strategies to establish infections, including the secretion of extracellular enzymes that act as potent virulence factors. These enzymes facilitate bacterial colonization of host tissues and help evade immune surveillance. By targeting structural components of host tissues and interfering with immune mechanisms, these enzymes play a pivotal role in disease progression.Extracellular Enzymes Facilitating Tissue Invasion: Several bacterial pathogens secrete...
01:12Bacterial Toxins
Bacterial toxins are sophisticated virulence factors that enable pathogenic bacteria to interact with, invade, and damage host tissues. These toxins fall broadly into two types: protein exotoxins, which are secreted into the environment and target specific host receptors, and lipopolysaccharide endotoxins, which are structural components of the bacterial outer membrane released primarily during bacterial lysis or membrane shedding. Exotoxins generally act more selectively, binding to cell...
01:20Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
01:31Defense Against Bacterial Pathogens
The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:28Regulation of Bacterial Virulence
Pathogenic bacteria employ a range of regulatory mechanisms to modulate the expression of virulence genes in response to environmental and host-derived signals. These mechanisms ensure that virulence factors are expressed only under favorable conditions, thereby optimizing infection and survival strategies.Mechanisms of Virulence RegulationKey regulatory strategies include:Two-Component Systems: These consist of a membrane-bound sensor kinase and a cytoplasmic response regulator. Environmental...