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Breaching the defence barricades; how Salmonella typhimurium fools the host
▶ Liu JZ, Jellbauer S, Poe AJ, et al. Zinc sequestration by the neutrophil protein calprotectin enhances Salmonella growth in the inflamed gut. Cell Host Microbe 2012;11:227–39.
Strategies employed by host organisms in response to bacterial infection are multi-faceted with the ultimate aim of inhibiting bacterial growth. One such response includes limiting the availability of essential metal ions, a process known as nutritional immunity. However, with the exception of iron, the role of metal sequestration in response to pathogens is not thoroughly understood. Neutrophils are innate immune cells that counter pathogens by many mechanisms, including release of antimicrobial proteins such as calprotectin to inhibit bacterial growth. Calprotectin sequesters essential micronutrient metals such as zinc, thereby limiting availability to microbes. This paper by Liu and colleagues uses a series of in vitro and in vivo approaches to demonstrate that while calprotectin is induced by neutrophils during infection with the gut pathogen Salmonella typhimurium, it does not inhibit S typhimurium proliferation. How can this microbe escape this defence mechanism? Remarkably, S typhimurium overcomes the antimicrobial defence of calprotectin-mediated zinc chelation by expressing a high affinity zinc transporter (ZnuABC). This allows the bacteria to acquire its essential metal despite a calprotectin induced famine in the surrounding microenvironment. ZnuABC was also required to promote the growth of S typhimurium over that of competing commensal bacteria. The findings indicate that Salmonella thrives in a neutrophil enriched environment by overcoming the zinc sequestration of calprotectin and highlights the importance of zinc acquisition in bacterial intestinal colonisation. The study also underlines the acquisition of the micronutrient zinc in the inflamed gut as an important means of growth and competition between microbes. The authors conclude by suggesting that targeted therapy to this metal acquisition system may offer a novel therapeutic strategy towards gut pathogens.
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