Abstract
Iron is an essential nutrient for many bacteria. Since the metal is highly sequestered in host tissues, bound predominantly to heme, pathogenic bacteria often take advantage of heme uptake and degradation mechanisms to acquire iron during infection. The most common mechanism of releasing iron from heme is through oxidative degradation by heme oxygenases (HOs). In addition, an increasing number of proteins that belong to two distinct structural families have been implicated in aerobic heme catabolism. Finally, an enzyme that degrades heme anaerobically was recently uncovered, further expanding the mechanisms for bacterial heme degradation. In this analysis, we cover the spectrum and recent advances in heme degradation by infectious bacteria. We briefly explain heme oxidation by the two groups of recognized HOs to ground readers before focusing on two new types of proteins that are reported to be involved in utilization of heme iron. We discuss the structure and enzymatic function of proteins representing these groups, their biological context, and how they are regulated to provide a more complete look at their cellular role.
Highlights
In the late 1960s, Tenhunen and colleagues isolated the first heme oxygenase, heme oxygenases (HOs)-1 (Tenhunen et al, 1968, 1969)
While the enzyme was discovered in rats, HO-1 is highly conserved in mammals
Research showed that heme is cleaved to generate the linear tetrapyrrole biliverdin, which is subsequently reduced to bilirubin by biliverdin reductase
Summary
In the late 1960s, Tenhunen and colleagues isolated the first heme oxygenase, HO-1 (Tenhunen et al, 1968, 1969). While oxidative cleavage by a HO or breakdown by coupled oxidation is achieved by two separate mechanisms, they cannot be discriminated based on their products alone as they both yield CO and verdoheme (which is hydrolyzed to biliverdin under acidic or alkali conditions) Because of this complexity and since proteins that exhibit heme degradation in vitro (in the presence of a reductant) may have another function under physiological conditions, it was suggested that a comprehensive approach that combines genetics, mechanistic enzymology, and metabolite profiling is necessary for the characterization these proteins before terming them HOs (Wilks and Ikeda-Saito, 2014). Oxidative degradation by HOs is the most common mechanism used to liberate iron from heme, other mechanisms have been discovered
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