ISSN 2519-8289 (Online)
During the past half century, research and clinical observations have revealed a vigorous competition for growth-essential iron between bacterial, fungal, and protozoan pathogens and their vertebrate hosts. The latter possess an array of mechanisms (collectively termed nutritional immunity) to withhold iron; the ability of microorganisms to overcome these mechanisms is an important component of virulence. Various aspects of nonspecific and immune defenses are impaired in severely iron-deficient hosts, whereas nutritional immunity is stressed in a diversity of conditions of iron overload. A number of possible methods and agents for suppressing or enhancing various facets of the influence of iron on infection are now apparent. Research is needed to determine which of these might be safe, efficacious, and practical.
All living cells have a quantitatively similar need for iron, and all must form or be supplied with compounds that they can use to solubilize and transport the metal. Proteins such as transferrin and lactoferrin that are employed for these functions by mammalian and avian hosts can, to some extent, withhold the metal from the siderophores of invading bacteria and fungi. To reinforce this withholding process, invaded hosts promptly become hypoferremic by halting intestinal assimilation of iron, and by increasing liver storage of the metal. The concomitant development of fever by hosts may serve to exacerbate the iron famine of the invaders inasmuch as synthesis of microbial siderophores is restricted by elevated temperatures. However, if hosts are hyperferremic (because of liver destruction, hemolytic diseases, neonatal status, or excess iron introduced by way of diet or injection) or hypotransferrinemic (as in kwashiorkor), they are exceedingly susceptible to even a small number of invading bacterial or fungal pathogens. The attempt by hosts to withhold iron from invaders is termed 'nutritional immunity'; the concept may embrace such other nutrilites as P(i) and zinc. Nutritional immunity might also be a component of defense against growth of tumor cells. As adjuncts to both antimicrobial and antitumor chemotherapy, it might be possible to use clinical procedures to strengthen nutritional immunity.
To successfully sustain an infection, nearly all bacteria, fungi and protozoa require a continuous supply of host iron.
Mechanisms of microbial iron acquisition are determinants for the kinds of cells, tissues and hosts in which pathogens can flourish. As a corollary, hosts possess an array of iron withholding devices whereby they can suppress or abort microbial invasions.
Awareness of environmental and behavioral methods that can prevent iron loading plus development of pharmaceutical agents that can block microbial access to iron may help to reduce our dependence on antibiotics.