Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations.

S aureus colonization (including MRSA) was extremely common in this cohort of maternal-infant pairs. Infants born to mothers with staphylococcal colonization were more likely to be colonized, and early postnatal acquisition appeared to be the primary mechanism.

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The S. aureus colonization rate is higher than previously reported and fluctuated over time in this prospective cohort of athletes. The higher colonization prevalence during summer might explain the infectious outbreak during the summer months and may represent a key intervention time for preventing S. aureus disease in athletes.

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