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Title: The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System
Abstract

Chronic infection withHelicobacter pyloriincreases risk of gastric diseases including gastric cancer. Despite development of a robust immune response,H. pyloripersists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection withH. pyloristrains which encode thecagType IV Secretion System (cag T4SS). ThecagT4SS 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 toH. pyloriinfection, the host produces a variety of antimicrobial molecules, including the iron‐binding glycoprotein, lactoferrin. Our work shows that apo‐lactoferrin exerts antimicrobial activity againstH. pyloriunder iron‐limited conditions, while holo‐lactoferrin enhances bacterial growth. CulturingH. pyloriin the presence of holo‐lactoferrin prior to co‐culture with gastric epithelial cells, results in repression of thecag T4SS activity. Concomitantly, a decrease in biogenesis ofcag 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 ofH. pylori‐related disease.

 
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Award ID(s):
1547757
NSF-PAR ID:
10273385
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
ChemBioChem
Volume:
22
Issue:
18
ISSN:
1439-4227
Page Range / eLocation ID:
p. 2783-2790
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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