The role of host heme in bacterial infection

Heme is an indispensable cofactor for almost all aerobic life, including the human host and many bacterial pathogens. During infection, heme and hemoproteins are the largest source of bioavailable iron, and pathogens have evolved various heme acquisition pathways to satisfy their need for iron and heme. Many of these pathways are regulated transcriptionally by intracellular iron levels, however, host heme availability and intracellular heme levels have also been found to regulate heme uptake in some species. Knowledge of these pathways has helped to uncover not only how these bacteria incorporate host heme into their metabolism but also provided insight into the importance of host heme as a nutrient source during infection. Within this review is covered multiple aspects of the role of heme at the host pathogen interface, including the various routes of heme biosynthesis, how heme is sequestered by the host, and how heme is scavenged by bacterial pathogens. Also discussed is how heme and hemoproteins alter the behavior of the host immune system and bacterial pathogens. Finally, some unanswered questions about the regulation of heme uptake and how host heme is integrated into bacterial metabolism are highlighted.