“Dynamic and mechanisms of early life interactions between bacteriophage and its bacteria host in the skin”

• Applicant: Dr. Mercedes Gomez de Agüero
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 465341196

Neonates rely on a competent skin barrier to deal with environmental challenges, including pathogens. Staphylococcus epidermidis is a major constituent of the human skin microbiota and acts as a barrier against colonization of pathogenic microbes. Recently, S. epidermidis has emerged as major agent causing neonatal sepsis, especially in preterm. Whilst term infants harbor commensal strains, preterm infants harbor in their skin strains of S. epidermidis with pathogenic elements, high ability to form biofilms and antibiotic resistant cassettes. Naturally, intact skin prevents pathogen penetration, but it constitutes a stockage niche. Disruptions of skin integrity caused by i.e. indwelling catheters allows penetration of S. epidermidis into the blood leading to sepsis in the case of pathogenic strains. SEP1 is a virulent bacteriophage hosted specifically by S. epidermidis1. Whilst SEP1 has broad lytic spectrum, some strains of S. epidermidis, although infected, remains resistant to the lysis. The aim of the project is to investigate the phage-host interaction in the neonatal skin. The objective are: i) to understand via which mechanism and under which condition the lifecycle of the phage are shaped by the microbiota and ii) study the impact of the bacteriophage in the microbial composition and function. Our hypothesizes are that the fitness and environmental adaptation of the commensal strains to the mature skin would prevent their lysis by the phages and that the phage would prevent the colonization of the skin by pathogenic strains of S. epidermidis by lysing them or by interfering with its pathogenicity. We will use a novel and unique experimental murine model developed in my lab to control skin maturation during the pregnancy with sterile offspring2. Commensal and pathogenic S. epidermidis isolates have been obtained from human neonatal skin and blood. We seek to study the behavior of the phage and the bacteria isolates in mature and immature skin using culture-based analysis, qPCR, NGS and metabolomic. We are interested in determining whether and how the bacteria could acquire resistance to the phage. We seek to investigate the potential interference and mechanisms of the phage in the niche competition of the commensal and pathogenic strains of the mature and immature skin. Finally, we will analyze the impact of phage in the pathogenicity of S. epidermidis in a model of sepsis. Our results will directly impact on the development of new strategies to treat preterm babies in order to prevent sepsis by pathogenic Staphylococcus epidermidis and beyond that will lay the framework to modulate colonization by multiresistant bacteria.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2330: New concepts in prokaryotic virus-host interactions - from single cells to microbial communities
• International Connection: Portugal
• Cooperation Partner: Dr. Luis Melo