Role and regulation of heme iron acquisition in gram-negative pathogens

Abstract

Bacteria that reside in animal tissues and/or cells must acquire iron from their host. However, almost all of the host iron is sequestered in iron-containing compounds and proteins, the majority of which is found within heme molecules. Thus, likely iron sources for bacterial pathogens (and non-pathogenic symbionts) are free heme and heme-containing proteins. Furthermore, the cellular location of the bacterial within the host (intra or extracellular) influences the amount and nature of the iron containing compounds available for transport. The low level of free iron in the host, coupled with the presence of numerous different heme sources, has resulted in a wide range of high-affinity iron acquisition strategies within bacteria. However, since excess iron and heme are toxic to bacteria, expression of these acquisition systems is highly regulated. Precise expression in the correct host environment at the appropriate times enables heme iron acquisitions systems to contribute to the growth of bacterial pathogens within the host. This mini-review will highlight some of the recent findings in these areas for gram-negative pathogens.

Keywords: Fur; hem; heme; hemin; hemoglobin; iron; pathogens; regulation.

Figure 1

Mechanisms for heme iron acquisition from the host by gram-negative bacteria. Bacteria factors damage host cells releasing heme, Hb, and other hemoproteins. Additionally, secreted bacterial hemophores capture host heme. Extracellular host Hb and heme may be bound by host Hp and Hpx, respectively. A bacterium could acquire iron from these host heme sources using one or more TonB-dependent outer membrane (OM) receptors for these heme compounds, which transport the heme through the outer membrane into the periplasm. Some OM receptors are specific for one molecule, whereas others have a broad specificity for multiple hemoproteins. Transport though the periplasmic and across the inner membrane is facilitated by ABC transport systems (green). Inside the bacterium, the heme is degraded using heme oxidases or stored in heme storage protein. Intracellular pathogens would have access to host heme and hemoproteins via similar mechanisms. cyto, bacterial cytoplasm; IM, bacterial inner/cytoplasmic membrane; OM, bacterial outer membrane. Although all the OMR are TonB-dependent, TonB is not shown in the figure.