Common Mechanisms of Bacterial Metal Homeostasis

Excerpt

Transition metals are required for the function of nearly half the enzymatic machinery of organisms. This is particularly challenging for bacteria, which move through environments in which metal levels can vary by orders of magnitude. Exacerbating the situation is the fact that metals easily compete for enzyme-binding sites, with inappropriate metallation typically inhibiting enzyme function. Thus microbes work hard to acquire, balance, and sort their metal pools. This chapter surveys the common tactics by which bacteria control intracellular iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn). The focus is on Escherichia coli, for which enough information is available to attempt an integrated view. High-affinity import systems are regulated at the level of transcription by specific metal-sensing transcription factors; posttranslational controls have not yet been identified. If these importers are insufficient, then metal-sparing strategies are engaged for iron and zinc, the two metals that are needed to activate essential enzymes. At the other extreme, metal overload can result in chemical injuries (Fe, Zn, Cu) and the mismetallation of noncognate enzymes (Fe, Zn, Mn). Export systems are induced to avoid these outcomes. Underlying the entire situation is the question of whether metals are sorted among enzymes by thermodynamic affinities or whether chaperone systems override binding strengths. At present the author infers that Cu movement may sometimes be chaperone driven, but that the other metals reversibly sample protein binding sites and populate them according to the relative binding strengths of proteins and competing metabolite ligands. This conclusion emphasizes that metal pool sizes must be controlled and balanced.