On the heme sensing system of Gram-positive bacterial pathogens
The human pathogen Staphylococcus aureus is capable of acquiring heme during infection for use as a source of iron, a nutrient that is scarce in its free form in host tissues. However, heme acquisition is dangerous to bacteria due to the toxicity of the heme molecule. We have found that S. aureus solves the heme paradox by sensing heme toxicity through the novel HssRS two-component system, which induces the expression of a transporter essential for overcoming the lethal effects heme exerts on staphylococci. In vitro and in vivo studies of HssRS signaling as well as a small molecule library screen for HssRS activators have provided insights into the signaling events regulating heme resistance in S. aureus. Furthermore, we have found that heme sensing through HssRS also occurs in Bacillus anthracis, the causative agent of anthrax. Our findings indicate that heme sensing may also occur throughout the life cycles of a number of other related Gram-positive bacteria. Together, these studies reveal the functional details of a novel bacterial heme detoxification system conserved among multiple Gram-positive bacteria that associate with host tissues rich in heme.