The Fate of Intracellular Metal Ions in Microbes

Microbes must acquire metals for metabolic processes, with nearly a half of all enzymes requiring a metal cofactor for function, yet microbes can be poisoned by metals. The host innate immune defenses are thought to exploit these vulnerabilities to protect against invading pathogens, whereas microbes can respond by employing multiple strategies to maintain their metal homeostasis. Understanding these microbial strategies combined with knowledge of diverse metal challenges faced by different microbes in the various host niches could inform the development of new approaches for combating infectious diseases. This chapter summarizes extensive discussions on the interplay of metal ions in host–microbe interactions, from the microbial perspective. Focus is on five key areas: (a) how we define and determine metal availability, (b) the different levels and sources of metals available to microbes in different niches within the host, (c) the effect of the metal status of a pathogen, as derived from its prior environment, on its ability to establish an infection or the severity of disease, (d) the interplay between metals and the microbiota, and (e) how metal restriction and metal oversupply can kill or inhibit the growth of microbes.