Question

Iron is an important item for the growth of microorganisms in a pathogenic state in the human body. Describe two ways in which bacteria might attempt to obtain iron from human cells or tissues for their own use. Then, describe a way in which this bacterial iron-scavenging might be disrupted without harming the human cells/tissues in the process.

Answer 1

Two ways in which bacteria might attempt to obtain iron from human cells or tissues for their own use are:

• ​​Nonheme iron acquisition systems: It involve the production and secretion of high-affinity siderophores that, are able to bind free iron ions, and are able to extract iron from mammalian iron binding proteins and deliver it to specific outer membrane receptors or lipoproteins.
• example of siderophore-mediated iron acquisition: Yersiniabactin system of Yersinia pestis, it is able to extract iron from mammalian transferrin and lactoferrin proteins and deliver it to a specific outer membrane protein.
• And alternative strategy to siderophore-mediated iron uptake is the utilization of outer membrane receptors that directly recognize mammalian iron-binding proteins, such as transferrin and lactoferrin proteins. Neisse has a set of transferrin-binding proteins (TbpA and TbpB) regarding the acquisition of iron from human transferrin. TbpA is a Ton-dependent receptor that binds the C-terminal lobe of transferrin, where it extracts iron through a distortion of the iron-binding site and transports it across the outer membrane. TbpA alone is sufficient for transferrin utilization, but the coreceptor TbpB enhances the efficiency of uptake by binding transferrin and increasing its concentration for subsequent utilization by TbpA.
• Heme acquisition system : In this, most commonly, there is direct uptake of heme by a cell surface receptor which binds heme or host hemoproteins. A variation of this method includes bipartite systems in which a lipoprotein facilitates heme or hemoproteins binding to the cell surface receptor. Alternatively, some pathogens produce hemophores, small secreted proteins that capture free heme or heme bound to host hemoproteins and then deliver this heme to bacterial surface receptors.

A way in which this bacterial iron-scavenging might be disrupted without harming the human cells in the process can be explained as:

The iron acquisition strategies by bacterial pathogens affect the host’s basal iron homeostasis for successful defense. A marked change in iron metabolism is a central component of a larger systemic host response to infection(inflammation, and cancer), collectively termed the acute-phase response (APR). The acute-phase responses is initiated by innate immune system to neutralize the source of infection or injury.

The acute-phase response markedly alters host iron metabolism in ways that serve to minimize iron bioavailability to pathogens. These include

(i) decreased iron release into the circulation (for which the acute phase protein mediator is hepcidin)

(ii) increased intracellular iron storage (for which the acute phase protein mediator is ferritin)

(iii) decreased accessibility of extracellular nonheme iron (for which the acute phase protein mediators are ceruloplasmin and lactoferrin)

(iv) decreased accessibility of extracellular heme iron (for which the acute phase protein mediators are hemopexin and haptoglobin).