The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System. (8th July 2021)

• Record Type: Journal Article
• Authors: Lu, Jacky; Haley, Kathryn P.; Francis, Jamisha D.; Guevara, Miriam A.; Doster, Ryan S.; Craft, Kelly M.; Moore, Rebecca E.; Chambers, Schuyler A.; Delgado, Alberto G.; Piazuelo, Maria Blanca; Damo, Steven M.; Townsend, Steven D.; Gaddy, Jennifer A.
• Is Part Of: Chembiochem. Volume 22:Number 18(2021)
• Page Start: 2783
• Page End: 2790
• Publication Date: 2021-07-08
• Subjects: antimicrobial -- bacterial pathogenesis -- glycobiology -- Helicobacter pylori -- host-pathogen interactions -- innate immunity -- iron homeostasis -- lactoferrin -- toxin secretion -- virulence; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202100249
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H . pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H . pylori strains which encode the cag Type IV Secretion System ( cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro‐inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H . pylori infection, the host produces a variety of antimicrobial molecules, including the iron‐binding glycoprotein, lactoferrin. Our work shows that apo‐lactoferrin exerts antimicrobial activity against H . pylori under iron‐limited conditions, while holo‐lactoferrin enhances bacterial growth. Culturing H . pylori in the presence of holo‐lactoferrin prior to co‐culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host‐pathogen interface was observed under these culture conditions by high‐resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro‐inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H . pylori ‐related disease. Abstract : Helicobacter pylori infection results in enhanced host production of lactoferrin which participates in nutritional immunity and can also serve as a source of nutrient iron for this pathogen, which can repress a major oncogenic virulence factor, the cag T4SS.