Heme Uptake and Metabolism in Bacteria

Abstract

All but a few bacterial species have an absolute need for heme, and most are able to synthesize it via a pathway that is highly conserved among all life domains. Because heme is a rich source for iron, many pathogenic bacteria have also evolved processes for sequestering heme from their hosts. The heme biosynthesis pathways are well understood at the genetic and structural biology levels. In comparison, much less is known about the heme acquisition, trafficking, and degradation processes in bacteria. Gram-positive and Gram-negative bacteria have evolved similar strategies but different tactics for importing and degrading heme, likely as a consequence of their different cellular architectures. The differences are manifested in distinct structures for molecules that perform similar functions. Consequently, the aim of this chapter is to provide an overview of the structural biology of proteins and protein-protein interactions that enable Gram-positive and Gram-negative bacteria to sequester heme from the extracellular milieu, import it to the cytosol, and degrade it to mine iron.

The Hemophore HasA from Yersinia pestis (HasAyp) Coordinates Hemin with a Single Residue, Tyr75, and with Minimal Conformational Change

“…The very low concentrations of free iron in host cells pose significant challenges to pathogenic bacteria, which have evolved efficient strategies to scavenge iron, including secretion of hemophores, siderophores, hemolysins, proteases and cytotoxins (1, 2). Given that ~70% of total iron is bound to hemoglobin, heme is an important iron source.…”

“…Given that ~70% of total iron is bound to hemoglobin, heme is an important iron source. Thus, a strategy used by bacteria to acquire heme is the deployment of hemophores, which are outer membrane-exposed, or secreted proteins involved in the path of heme transfer from their location in the host to the bacterial cytosol (2, 3), where the macrocycle is degraded by heme-degrading enzymes to release the iron (1, 4, 5). The HasA-type hemophore was first identified in Serratia marcescens (6) and then shown to be conserved in several Gram negative pathogens including, Pseudomonas aeruginosa , Pseudomonas fluorescens, Yersinia pestis , Yersinia pseudotuberculosis , Erwinia carotovora and Pectobacterium carotovorum (7–11).…”

In vitro heme biotransformation by the HupZ enzyme from Group A streptococcus

“…Pathogenic bacteria often tap into the heme reservoir to overcome the severe iron scarcity, which they encounter during infection. These pathogens use elaborate systems to scavenge heme from host hemoproteins and transport it into the bacterial cell (Benson and Rivera 2013;Mayfield et al 2011;Nobles and Maresso 2011;Pishchany and Skaar 2012). A few mechanisms allow bacteria to retrieve iron from heme.…”

Haem Biosynthesis and Uptake in Schistosoma mansoni

“…The haem acquisition system in bacteria has been extensively researched (Benson and Rivera, 2013). In bacteria, unique surface receptor proteins mediate the scavenging of host haem through the binding to haem or haemophores (Benson and Rivera, 2013).…”

“…The haem acquisition system in bacteria has been extensively researched (Benson and Rivera, 2013). In bacteria, unique surface receptor proteins mediate the scavenging of host haem through the binding to haem or haemophores (Benson and Rivera, 2013). A similar system of haem-binding proteins for the acquisition of haem, in association with surface receptor protein was also found in R. prolixus and many haematophagous insects (Donohue et al, 2009;Gudderra et al, 2001).…”