# Characterising commensal and pathogenic staphylococcal interactions with neonatal and adult blood

## TL;DR

This study explores how preterm infants, term infants, and adults respond differently to staphylococcal infections, revealing unique immune and bacterial gene activity patterns.

## Contribution

The study uses dual RNA-seq to uncover age-specific immune and bacterial gene responses in neonatal and adult sepsis models.

## Key findings

- Shared immune responses across age groups include cytokine and chemokine signaling upon bacterial challenge.
- Preterm infants uniquely activate platelet and fibrin pathways, Wnt signaling, and hypoxia in response to S. epidermidis.
- Host developmental age influences bacterial gene co-expression, including iron acquisition and heme biosynthesis.

## Abstract

The abundant skin commensal, Staphylococcus epidermidis, is the leading cause of late-onset sepsis (LOS) in preterm infants but rarely causes infections in term infants and adults. Staphylococcal virulence mechanisms and the role of the preterm immune responses in driving these life-threatening infections remain poorly understood. Using an ex vivo sepsis model, we challenged whole blood from very preterm infants (30–32 weeks gestational age, GA; n = 8), term infants (> 37 weeks GA; n = 8), and young adults (18–25 years; n = 8) with either live S. epidermidis or S. aureus (~ 107 colony-forming units, CFU/ml) for 90 min. Dual RNA-sequencing (RNA-seq) was performed to simultaneously assess host and pathogen gene expression profiles, identifying common and pathogen-specific responses across cohorts. We found shared immune processes induced in all age groups upon bacterial challenge, including cytokine (IL1A, IL1B, IL6, IFNB1) and chemokine (CCL20, CCL3, CCL7, CXCL2) signalling. Preterm infants also exhibited unique responses, such as increased platelet activation and fibrin clot formation, Wnt signalling, and hypoxia pathways in response to S. epidermidis challenge. Our findings suggest that bacterial gene co-expression, including iron acquisition and heme biosynthesis genes, are also influenced by the hosts developmental age, highlighting the complexity of host-bacterial interactions in the early stages of neonatal sepsis.

The online version contains supplementary material available at 10.1038/s41598-025-30393-8.