Abstract

Iron is a transition metal utilized by nearly all forms of life for essential cellular processes, such as DNA synthesis and cellular respiration. During infection by bacterial pathogens, the host utilizes various strategies to sequester iron in a process termed, nutritional immunity. To circumvent these defenses, Gram-negative pathogens have evolved numerous mechanisms to obtain iron from heme. In this review we outline the systems that exist in several Gram-negative pathogens that are associated with heme transport and utilization, beginning with hemolysis and concluding with heme degradation. In addition, Gram-negative pathogens must also closely regulate the intracellular concentrations of iron and heme, since high levels of iron can lead to the generation of toxic reactive oxygen species. As such, we also provide several examples of regulatory pathways that control heme utilization, showing that co-regulation with other cellular processes is complex and often not completely understood.

Highlights

  • Iron is a transition metal that is essential for Gram-negative pathogen growth and successful colonization of a host (Palmer and Skaar, 2016; Sheldon et al, 2016)

  • Since iron is required for growth by many bacteria, animal hosts utilize multiple iron sequestering molecules to limit freeiron availability and combat pathogen colonization

  • Much of the research in this area has focused on how Gram-positive pathogens, especially S. aureus, acquire iron from these sources; it is becoming increasingly apparent that Gram-negative bacteria can acquire iron from heme during infection

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Summary

Introduction

Iron is a transition metal that is essential for Gram-negative pathogen growth and successful colonization of a host (Palmer and Skaar, 2016; Sheldon et al, 2016). During infection by pathogenic organisms, including Gram-negative bacteria, the availability of free-iron is targeted by the host immune response (Palmer and Skaar, 2016). The FeoB protein from E. coli binds and transports ferrous iron across the outer membrane and FeoB homologs have been identified in several bacterial pathogens, including Campylobacter jejuni (Naikare et al, 2006).

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