Heme acquisition and tolerance in Gram-positive model bacteria: An orchestrated balance

As a nutrient, heme is important for various cellular processes of organism. Bacteria can obtain heme via heme biosynthesis or/and uptake of exogenous heme from the host. On the other side, absorption of excess heme is cytotoxic to bacteria. Thus, bacteria have developed systems to relieve heme toxicity and contribute to the maintenance of heme homeostasis. In the past decades, the mechanisms underlying heme acquisition and tolerance have been well studied in Gram-positive model bacteria, such as Staphylococcus, Streptococcus and other Gram-positive bacteria. Here, we review the elaborate mechanisms by which these bacteria acquire heme and resist heme toxicity. Since both the heme utilization system and the heme tolerance system contribute to bacterial virulence, this review is not only helpful for a comprehensive understanding of the heme homeostasis mechanism in Gram-positive bacteria but also provides a theoretical basis for the development of antimicrobial agents.