MicrobiologyBytes

Iron is required for many cellular processes, but can be toxic at high concentrations. Thus iron homeostasis is strictly regulated so that iron acquisition, storage, and consumption are geared to iron availability, and that intracellular levels of free iron do not reach toxic levels. Recently, the roles of manganese and its control in cells have been investigated, and it is becoming clear that some aspects of the metabolism of iron and manganese are interrelated.

Control of bacterial iron homeostasis by manganese. PNAS USA May 24 2010. doi: 10.1073/pnas.100234210
Perception and response to nutritional iron availability by bacteria are essential to control cellular iron homeostasis. The Irr protein from Bradyrhizobium japonicum senses iron through the status of heme biosynthesis to globally regulate iron-dependent gene expression. Heme binds directly to Irr to trigger its degradation. Here, we show that severe manganese limitation created by growth of a Mn2+ transport mutant in manganese-limited media resulted in a cellular iron deficiency. In wild-type cells, Irr levels were attenuated under manganese limitation, resulting in reduced promoter occupancy of target genes and altered iron-dependent gene expression. Irr levels were high regardless of manganese availability in a heme-deficient mutant, indicating that manganese normally affects heme-dependent degradation of Irr. Manganese altered the secondary structure of Irr in vitro and inhibited binding of heme to the protein. We propose that manganese limitation destabilizes Irr under low-iron conditions by lowering the threshold of heme that can trigger Irr degradation. The findings implicate a mechanism for the control of iron homeostasis by manganese in a bacterium.

Related:

• Iron Uptake and Virulence
• How bacteria capture iron from heme
• Utilization of iron by Campylobacter jejuni

Heme is ubiquitous, abundant, and vitally necessary as a cofactor in oxidoreduction and gas transport. Most microorganisms display a complete heme biosynthetic pathway, but are able to acquire the essential ferrous iron from exogenous heme. Free heme or heme arising from hemoproteins is internalized intact and subsequently degraded in the cytosol. Diverse mechanisms for heme uptake have been identified in bacteria. They involve extracellular hemoproteins (hemophores) that capture heme and deliver it to bacteria and cell surface receptors that bind heme, hemoproteins, and/or hemophores. Surface receptors of Gram-positive bacteria are cell-wall anchored proteins that scavenge heme and relay it to specific ABC transporters involved in heme internalization. The absence of these newly identified mechanisms from higher eukaryotic organisms makes them potential targets for new antibacterial drugs, especially since there is growing evidence that heme utilization systems are required for bacterial virulence.

Bacteria capture iron from heme by keeping tetrapyrrol skeleton intact. PNAS USA June 29, 2009, doi: 10.1073/pnas.0903842106
Because heme is a major iron-containing molecule in vertebrates, the ability to use heme-bound iron is a determining factor in successful infection by bacterial pathogens. Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli. YfeX is located in the cytoplasm. EfeB is periplasmic and enables iron extraction from heme in the periplasm and iron uptake in the absence of any heme permease. YfeX and EfeB are widespread and highly conserved in bacteria. We propose that their physiological function is to retrieve iron from heme.

Related:

• Iron Uptake and Virulence
• New drug targets for urinary tract bacterial infections
• Bacillus anthracis gets iron from hemoglobin
• Utilization of iron by Campylobacter jejuni
• Bacterial sensors of oxygen