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.
Completed project
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.
Project partners
- Jonas Warringer, University of Gothenburg, Sweden (Coordinator)
- Edward Moore, University of Gothenburg, Sweden
- Gianni Liti, University of Nice, France
- Danesh Moradigaravand, The Wellcome Trust Sanger Institute, United Kingdom
- Jan Michiels, University of Leuven, Belgium
- Anne Farewell, University of Gothenburg, Sweden
- Ville Mustonen, The Wellcome Trust Sanger Institute, United Kingdom
Project resources
- Studies on Symbiotic and pathogenic interactions from Jan Michiels group
- CARe – Centre for Antibiotic Resistance Research at University of Gothenburg
- The Problem of Antibiotic Resistance: An Open Education Resource
Tools
The manuscript that marks the release of the genomics and phenotypic resources and their global description is in preparation. Read more: github.com/matdechiara/TransPred
Publications
- bioRxiv, 2020. Genomic epidemiology and evolution of Escherichia coli in wild animals
- mSystems, December 2020. A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
- Scientific Reports, 2020. Complete genome sequences of Streptococcus pyogenes NCTC 8198T and CCUG 4207T, the type strain of the type species of the genus Streptococcus: 100% match in length and sequence identity between PacBio solo and Illumina plus Oxford Nanopore hybrid assemblies
- bioRxiv, 2018. Conjugation factors controlling F-plasmid antibiotic resistance transmissio
- Drug Development Research, 2018. Inhibiting conjugation as a tool in the fight against antibiotic resistance
- Plos Computational Biology, 2018. Prediction of antibiotic resistance in Escherichia coli from large-scale pan-genome data
- mSystems, 2021. Machine Learning Prediction of Resistance to Subinhibitory Antimicrobial Concentrations from Escherichia coli Genomes
- FEMS Microbiol Lett. 2020. Teaching about antibiotic resistance to a broad audience: a multidisciplinary approach.
- mSphere. 2021. Genomic Epidemiology and Evolution of Escherichia coli in Wild Animals in Mexico.
- Anal Chem. 2019. Chemical Changes On, and Through, The Bacterial Envelope in Escherichia coli Mutants Exhibiting Impaired Plasmid Transfer Identified Using Time-of-Flight Secondary Ion Mass Spectrometry.
