The human antimicrobial protein calgranulin C (S100A12) participates in control of Helicobacter pylori growth and regulation of virulence.

During infectious processes, antimicrobial proteins are produced by both epithelial cells and innate immune cells. Some of these antimicrobial molecules function by targeting transition metals and sequestering these metals in a process referred to as "nutritional immunity". This chelation strategy ultimately starves invading pathogens, limiting their growth within the vertebrate host. Recent evidence suggests that these metal-binding antimicrobial molecules have the capacity to affect bacterial virulence including toxin secretion systems. Our previous work showed that the S100A8/S100A9 heterodimer (calprotectin, calgranulin A/B), binds zinc and represses the elaboration of the H. pylori cag-T4SS. However, there are several other S100 proteins that are produced in response to infection. We hypothesized that the zinc-binding S100A12 (calgranulin C) protein is induced in response to H. pylori infection and also plays a role in controlling H. pylori growth and virulence. To test this we analyzed gastric biopsies from H. pylori-positive or -negative patients for S100A12 expression. These assays showed that S100A12 is induced in response to H. pylori infection and inhibits bacterial growth and viability in vitro by binding nutrient zinc. Furthermore, the data establish that the zinc-binding activity of the S100A12 protein represses the activity of the cag-T4SS as evidenced by gastric cell hummingbird phenotype, IL-8 secretion, and CagA translocation assays. In addition, high-resolution field emission gun scanning electron microscopy (FEG-SEM) was used to demonstrate that S100A12 represses biogenesis of the cag-T4SS. Together with our previous work, these data reveal that multiple S100 proteins can repress the elaboration of an oncogenic bacterial surface organelle.