Infectious Diseases

November 21, 2014

Host sequesters zinc to control stomach bug

Understanding how zinc and the host’s immune response control H. pylori’s cancer-causing potential could suggest new therapeutic strategies to reduce infection and cancer risk.

Graphic of H. pylori bacterium

Helicobacter pylori colonization of the stomach causes chronic inflammation and is a major risk factor for gastric cancer. H. pylori strains that produce the cag secretion system, which translocates the cancer-causing CagA protein into cells, are associated with increased inflammation and cancer risk.

In an October issue of PLOS Pathogens, first author Jennifer Gaddy, Ph.D., corresponding author Holly Algood, Ph.D., and colleagues recently demonstrate a role of the host protein calprotectin – a metal-sequestering protein produced by neutrophils – in modulating the H. pylori cag secretion system.

Using cultured cells, they demonstrated that calprotectin represses H. pylori secretion of CagA by binding and sequestering zinc. They found that mice missing calprotectin have more gastric inflammation after infection with H. pylori containing the cag secretion system, compared to control mice. No differences were observed in mice infected with strains of H. pylori that lack the secretion system.

These findings demonstrate that zinc and the host’s immune response play a role in modulating the H. pylori cag secretion system and could help us develop novel antimicrobial therapeutic strategies targeting secretory processes in H. pylori.

This research was supported by grants from the Department of Veterans Affairs and from the National Institutes of Health (AI039657, AI068009, DK058587, CA077955, CA116087, AI101171).

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