Born in the Twilight of Antibiotics - Fighting Antimicrobial Resistance in Preterm Infants

This project addresses the urgent need for new strategies to combat antimicrobial resistance. While antibiotics have saved millions of lives, the worldwide rise in antibiotic resistance give rise to thousands suffering and dying during the first days of life due to resistance of antibiotics. In addition to resistance during early life, antibiotic promote microbiome disruptions that can have life-long consequences, including among other conditions, increased risk of respiratory infections.

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The project is part of the Born in the twilight program, funded by the Olav Thon Foundation, with partners in Norway, Denmark and Sweden.

Olav Thon stiftelsen, logo
The project is funded by the Olav Thon Foundation

Aims

We aim to

  • gain insight into how the microbiome and the collection of resistance genes carried by the microbiome, the resistome, develop in preterm infants in response to different antibiotic interventions.
  • identify if disadvantageous developments of the microbiome can be prevented by supportive treatment with the recently described HAMLET-protein

The results are expected to

  • provide increased knowledge on human microbiome and resistance development,
  • develop new strategies to fight antibiotic resistance, and
  • provide information to better guide antibiotic use in preterm infants
Partner institutions are based in Copenhagen, Malmø and Oslo
Photo: colourbox.com

Progress

The group held its kick-off meeting at the University of Oslo on the 12th March, 2018, with representatives from Sweden and Denmark.

We have gained all the necessary approvals and collection of samples has started. In this longitudinal study, samples will be collected from preterm babies born in the period between 2019 and early 2021. 

  • We are working on the establishment of a model that aims to reproduce the microbiome of the respiratory tract of preterm babies in the laboratory.

This model will enable using the samples from the babies to test antibiotics alone or in combination with antimicrobials found in breast milk, for their effects on the microbiome.

  • The group has established the methodology to perform functional metagenomics.

Together with shotgun metagenomics, this method will enable the idenficiation of new and functional antibiotic restistance genes in the preterm babies.

Animal models

We are using neonatal mouse models to study the impact of clinically relevant antibiotic regimens on the infant microbiota and immune system. Specifically, we investigate:

  • how antibiotics alter the composition and diversity of the microbiota; and
  • how antibiotics modulate the innate and adaptive immune responses.       

An Analytical Tool

We are also working on the design of a analytical and visualization tool, the ResistoXlorer, that will be used in the project for characterization of the microbiome and the resistomes. ResistoXplorer is also intended to benefit the entire scientific community by launching it as an online tool that can be accessed by all, both clinicians and researchers and other interested parties, for better surveillance, monitoring and decision making for antibiotic usage and understanding of resistome development.

Research Group

The research group is represented by a distinctive combination of expertise in pediatric neonatology, infectious diseases, public health, molecular biology and microbiology: 

Research group at Institute of Oral Biology, Group photo
The research group at UiO: From top left: Polona Rajar, Roger Junges, Sudhanshu Shekhar, Achal Dhariwal,
​​​Bottom left: Anna Torwick, Rabia Khan, Fernanda Petersen, Gabriela Salvadori da Silva, Heidi Aarø Åmdal. 

Project Leader

Professor Fernanda Petersen, Department of Oral biology, UiO 

Partners in Denmark

Dr. Ulrik Lausten-Thomsen, Department of Neonatology at the Juliane Centre, Rigshospitalet, Copenhagen University Hospital, Denmark

Professor Gorm Greisen, professor of Paediatrics at the Department of Neonatology at the Juliane Centre, Rigshospitalet, Copenhagen University Hospital and the University of Copenhagen 

Partner in Sweden

Professor Anders Hakansson, Professor at Experimental Infection Medicine, Lund University, Malmö, Sweden

Partners in Norway

Dr Kirsti Haaland, Neonatology, Oslo University Hospital 

Prof. Dag Berild, Department of Infectious Diseases, Oslo University Hospital, and University of Oslo 

Prof. Ola Didrik Saugstad, Professor emeritus at Paediatric Research UiO and Oslo University Hospital 

Ulf Dahle, Specialist Director, Infection Control and Environmental Health, Norwegian Institute of Public Health 

Professor Thomas Kuntziger, Department of Oral biology, UiO

Researcher

Sudhanshu Shekhar, Department of Oral biology, UiO

Postdoctorate Fellows

Roger Junges, Department of Oral biology, UiO

Gabriela Salvadori Silva, Department of Oral biology, UiO

PhD Candidates

Achal Dhariwal, Department of Oral Biology, UiO, 

Polona Rajar, Department of Oral biology, UiO and OUS

Navdeep Kaur Brar, Department of Oral Biology, UiO

Head Engineer

Heidi Aarø Åmdal, Department of Oral Biology, UiO

Administration and coordination

Anna Torwick, Department of Oral Biology, UiO 

From the left: Polona Rajar collect samples from hospitals in Norway and study them in the laboratory. Achal Dhariwal works on the development of the ResistoNett, and Gabriela Salvadori da Silva works in the laboratory on the development of the functional metagenomics, shotgun sequencing and the development of techniques allowing us to study the resistance genes in the samples.
From the left: Polona Rajar, PhD candidate, Achal Dhariwal, PhD Candidate, Gabriela Salvadori da Silva, postdoctoral fellow

Funding

 

 

 

Additional Funding

Resispart

Tags: AMR, microbiome, premature infants, babies, antimicrobial resistance By Anna Torwick
Published July 16, 2020 11:15 AM - Last modified June 2, 2021 1:00 PM