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The Innate Immune Glycoprotein Lactoferrin Represses the Helicobacter pylori cag Type IV Secretion System
Author(s) -
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.
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202100249
Subject(s) - lactoferrin , caga , secretion , helicobacter pylori , biology , innate immune system , microbiology and biotechnology , immune system , pathogenicity island , inflammation , pathogen , immunology , virulence , biochemistry , gene , genetics
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.