H. pylori - Ace Infectious
Drug Development Targeting Immune Evasion Mechanisms of H. pylori
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Drug Development Targeting Immune Evasion Mechanisms of H. pylori

Ace Infectious provides drug development services targeting the immune evasion mechanism of H. pylori to help develop drugs that facilitate the elimination of H. pylori by the body. Since H. pylori vacuolating cytotoxin A (VacA), gamma-glutamyl transpeptidase (GGT), and cholesterol glycosyl-transferase (CGT) are associated with the immune evasive, currently, we offer drug development services targeting these molecules.

Drug development targeting VacA

VacA helps H. pylori achieve immune evasion by disrupting the physiological function and activity of immune cells. VacA can form anion-selective channels and has the vacuolating activity that has been reported to require oligomerization into single-layered structures (usually hexamers and heptamers) or double-layered structures (Fig. 1). Then, VacA usurps lysosomal, which interferes with antigen presentation by B cells. In addition, VacA inhibits the activation and proliferation of T and B cells, causes apoptosis of macrophages, and causes the expression of the pro-inflammatory enzyme COX-2 in macrophages and neutrophils. As mentioned above, VacA severely damages immune cells, and drug development against VacA is necessary.

Structural organization of water-soluble VacA oligomersFig. 1 Structural organization of water-soluble VacA oligomers (Foegeding et al., 2016).

Ace Infectious provides drug development services targeting VacA. Firstly, we offer small molecule drug development services targeting Sec-dependent cleavage and amino-terminal signal peptides to interfere with the formation of active form. Then we offer neutralizing antibody development services targeting the P55 domain of VacA to interfere with the binding of VacA to cells and offer neutralizing antibody development services targeting the P33 domain to interfere with the insertion of VacA into membranes. Furthermore, we provide drug development services for the inhibition of anion-selective channel pores formed by VacA.

Drug development targeting GGT

GGT helps H. pylori evade immunity in three ways. First, GGT blocks Ras MAPK-dependent signaling leading to the arrest of T cells in the G1 phase. Second, GGT inhibits the differentiation of dendritic cells. Third, it also causes the expression of the pro-inflammatory enzyme COX-2. In addition, GGT damages gastric epithelial cells leading to apoptosis and inflammation.

Effects of Helicobacter pylori gamma-glutamyl transpeptidase on T cell-mediated immunityFig. 2 Effects of Helicobacter pylori gamma-glutamyl transpeptidase on T cell-mediated immunity (Ricci et al., 2014).

We provide drug development services targeting GGT. We offer the development of drugs that affect the extracellular secretion and self-cleavage of GGT. Then, we provide drug development services for small molecules that inhibit the enzymatic activity of GGT. We also provide drug development services targeting its mechanism of stimulating Ras MAPK-dependent signaling.

Drug development targeting CGT

CGT relies on its enzymatic function to help H. pylori evade host immunity. CGT is the enzyme responsible for cholesterol glycosylation, which operates the autophagic process to damage macrophages, and regulates the T cell-dependent inflammatory responses. Furthermore, through CGT, H. pylori extract cholesterol from the host's gastric epithelial cells which damages the lipid valves.

Ace Infectious provides drug development services targeting H. pylori CGT to address H. pylori immune evasion and reduce its ability to colonize. Since CGT is enzymatically active only after separation from the membrane, we offer enzyme inhibitor development services targeting this state of CGT.

Contact us

Ace Infectious offers specialized drug development services targeting H. pylori immune evasion-related proteins, such as VacA, GGT, and CGT. If you need to develop drugs targeting H. pylori immune mechanisms, please contact us for one-stop drug development services.

References

  1. Foegeding, N. J.; et al. An overview of Helicobacter pylori VacA toxin biology. Toxins. 2016, 8(6): 173.
  2. Ricci, V.; et al. Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role. World J Gastroenterol. 2014, 20(3): 630-38
  3. Qaria, M. A.; et al. Cholesterol glucosylation–based survival strategy in Helicobacter pylori. Helicobacter. 2021, 26(2): e12777.

※ All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.