Project A03

Molecular decision points that determine colonisation and infection risk in neonatal skin

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Dr. Mercedes Gomez de Agüero

 

Biomass, diversity and the pathogenic or commensal nature of the microbial pioneers that colonise neonates are key elements for establishing the baseline of a tissue and for preventing infections. Tissue associated parameters, such as redox level, pH (natural moisturizing factors), nutrients (lipids) and antimicrobial molecules are important factors that determine microbial colonisation. Very little is known about which of these determinants drive the selection of skin colonisers in neonates. Staphylococcus epidermidis is a well-known commensal that colonises the skin at birth. Especially in preterm infants, where the skin barrier is frequently disrupted due to immaturity, inserted medical devices or wounds, opportunistic and increasingly drug-resistant S. epidermidis strains have emerged as the predominant agent causing neonatal sepsis. The aim of this proposal is to identify the molecular decision points in the host that directly or indirectly (through its microbiota) regulate early life skin colonisation. We hypothesize that the undifferentiated skin of preterm babies represents an environment that promotes colonisation by pathogenic S. epidermidis strains and we aim to characterise key parameters of the skin that control this colonisation. In particular, we will investigate chemical (antimicrobial peptides, RNases, free fatty acids, lipids, pH), niche (stratum corneum, keratinocyte layers, hair follicles), immunological (resident immune cells) and metabolic factors (glucose metabolism) that determine the barrier function of the skin. In addition, we will decipher whether these factors be modulated by postnatal colonisation. Restricting the reservoir of pathogens in the neonatal skin, without disturbing the developing physiological microbiota could be an ideal strategy to reduce neonatal sepsis and expansion of multidrug resistant microbes.