Introducti

Notes

Introduction The spread of antibiotic resistance amongst bacteria has led both the Centers for Disease Con- trol and Prevention and the World Health Organization to state that infections represent a serious threat to human health [1, 2]. This threat is exemplified by Staphylococcus aureus, a Gram-positive bacterium that asymptomatically colonizes one third of the population and is a leading cause of antibiotic-resistant infections [3–5]. A promising area of investigation is eluci- dating how pathogens overcome host defenses such as the active withholding of essential nutrients and the oxidative burst of immune cells. During infection, pathogens must obtain all of their nutrients from the host, including the essential metal ions that are needed for the approximately one-third of all bacterial proteins that require a metal cofactor [6–8]. This requirement is exploited by the host, which restricts the availability of these essential nutrients, a defense termed nutritional immunity [9–13]. The canonical example of nutritional immunity is the iron (Fe)-withholding response [10, 11]. In addition to Fe, the host also restricts the availability of manganese (Mn) and zinc (Zn) [9, 12– 14]. ...