Experimental evolution of <i>Staphylococcus aureus</i> in macrophages: dissection of a conditional adaptive trait promoting intracellular survival

Abstract

<i>Staphylococcus aureus</i> is an important human bacterial pathogen. The host response to <i>S. aureus</i> involves the production of innate immune cells such as macrophages which are important for fighting infection. Here we report a new model of experimental evolution for studying how <i>S. aureus</i> can evade killing by macrophages. We identified a novel adaptive phenotype that promotes survival in macrophages and blood and resistance to antibiotics. The phenotype is lost rapidly upon growth in nutrient-rich conditions via disruption of the alternative sigma factor sigB, revealing a conditional niche-specific fitness advantage. Genomic analysis of clinical isolates suggests similar adaptations may occur during human infections. Our model may be used broadly to identify adaptations of <i>S. aureus</i> to the innate immune response.