Bacterial Handling of Host Nutrients: the Iron Paradigm
from: Bacterial Pathogenesis: Molecular and Cellular Mechanisms (Edited by: Camille Locht and Michel Simonet). Caister Academic Press, U.K. (2012)
Pathogenic bacteria must compete with their host for iron. The host lowers serum iron levels during inflammation and binds iron with high affinity to transferrin and lactoferrin, thereby limiting iron availability for the pathogens. Under such iron-limiting conditions, many pathogens, like their non-pathogenic relatives, secrete iron chelators, called siderophores, which mobilize even traces of iron for the bacteria. The host combats catecholate siderophores of various pathogens by avidly binding the chelator to the host protein siderocalin. Pathogenic bacteria can evade this host mechanism in one or more ways: secreting other siderophores that are not bound by siderocalin, utilizing heme as an iron source, and transporting ferrous iron. All these uptake systems are regulated by the general iron needs of bacteria and fine tuned according to the surrounding supply of iron-containing compounds. Iron limitation is also a signal for many pathogens to produce toxins and other virulence factors. When one iron supply system is disabled, virulence is often only mildly attenuated. Although it has long been known that iron is required for the infection process, no therapeutics directed at this have been marketed yet read more ...