Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic Staphylococcus

Abstract

Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease. However, the consequences of hemoglobin evolution for bacterial nutrient acquisition remain unclear. Here we show that the - and {beta}-globin genes exhibit strikingly parallel signatures of adaptive evolution across simian primates. Rapidly evolving sites in hemoglobin correspond to binding interfaces of IsdB, a bacterial hemoglobin receptor encoded by pathogenic Staphylococcus aureus. Using an evolution-guided experimental approach, we demonstrate that divergence between primates and staphylococcal isolates governs hemoglobin recognition and bacterial growth. Reintroducing putative adaptive mutations in - or {beta}-globin proteins is sufficient to impair S. aureus binding, providing a mechanism for the evolution of disease resistance. These findings suggest that bacterial hemoprotein capture has driven repeated evolutionary conflicts with hemoglobin during primate descent.