Predicting cell-cell horizontal transmission of antibiotics resistance from genome and phenome

• Jonas Warringer, University of Gothenburg, Sweden (Coordinator)
• Edward Moore, University of Gothenburg, Sweden (Partner)
• Gianni Liti, University of Nice, France (Partner)
• Leopold Parts, The Wellcome Trust Sanger Institute, United Kingdom (Partner)
• Jan Michiels, Katholieke Universiteit Leuven, Belgium (Partner)
• Anne Farewell, University of Gothenburg, Sweden (Observer)
• Ville Mustonen, University of Helsinki, Finland (Observer)

Resistance to antibiotics, particularly in Gram-negative bacteria, is an accelerating health crisis. Only few new antibiotics against Gram-negatives are in clinical trials and resistance also to new antibiotics is predicted to spread rapidly upon clinical introduction. Horizontal transmission of antibiotic resistance factors within pathogenic species, combined with the selective pressure imposed by extensive antibiotic use that favours resistant strains, explains much of the accelerating antibiotics resistance crisis. We propose to disclose candidate drug targets controlling the horizontal cell-cell transmission of anti-microbial resistance and to predict AMR and its transmission dynamics from bacterial genome composition. We employ experimental evolution of Escherichia coli, one of the most problematic species, to experimentally identify genes controlling the plasmid transmission rates. The hope is that these will be good targets for developing drugs that slows antibiotics resistance development. We also sequence the genomes of many clinical bacterial isolates and mathematically and computationally disclose natural variants likely to affect plasmid transmission properties. We hope that this will lay the foundations for a future personalized medicine that tailors antibiotic choice to infection such that resistance development within each patient is delayed or avoided completely.

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