Predicting cell-cell horizontal transmission of antibiotics resistance from genome and phenome
TransPred is a collaborative research program, funded by the European Joint Programming Initiative for Antimicrobial Resistance, that seeks to understand genetic factors that controls the horizontal transmission of antibiotic resistance between gram negative bacteria and to disclose drug targets whose inhibition would slow the spread of antibiotics resistance. The program sequences E. coli strains isolated from animals, the environment and patients and measures their capacity to resist antibiotics and transfer this resistance to other strains. Genes and alleles explaining these properties are identified by genome-wide association analysis and machine learning predictions and confirmed in experiments.
Antibiotics resistance is an accelerating crisis in gram-negative bacteria. Horizontal transmission of antibiotic resistance factors combined with the selective pressure imposed by antibiotic use has facilitated a rapid spread of resistance between and within pathogenic bacterial species. 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. New approaches to this problem are sorely needed.
Antibiotic resistance factors promote exclusion, evasion or inactivation of antibiotics, e.g. by encoding efflux pumps or enzymes that degrade an antibiotic (Blair, et al, 2015). Horizontal transmission of resistance cassettes occurs predominantly by conjugative elements that are copied and then exchanged between cells during bacterial conjugation. Conjugative elements contain genes that carry much of the vital information needed for their transfer to new strains and some of these genes have been studied.
However, not all pairs of bacteria are equally likely to exchange conjugative elements carrying antibiotic resistance. Thus, variation in horizontal transmission depends not only on the genes carried by the conjugative elements but also on the genes on the chromosomes of the donor and recipient cells. Chromosomally encoded factors controlling horizontal transmission are likely to be less specific to particular conjugative elements and therefore to constitute better drug targets but are virtually unknown. The general lack of knowledge in this area means that we cannot design drugs to target horizontal transmission and we cannot predict how fast resistance to a particular antibiotic will spread in bacterial population, such as in an infection.
Note: The manuscript that marks the release of the genomics and phenotypic resources and their global description is in preparation. Please contact AF, GL and JW ( see below for contacts) if you are interested in using the data before they are formally release.
TransPred continuously releases E. coli sequence, antibiotics resistance and transmission of resistance data from strains accumulating in the project. The data is available to academic users provided that such users agree:
- Not to distribute the data to third parties
- Not to present or publish analysis of the data unless the data has been published in peer reviewed scientific journals by members of the consortium
- To reference the source of the data in a scientifically correct way when presented
- Antibiotic resistance data for the E. coli collection can be downloaded here: https://github.com/matdechiara/TransPred/tree/main/phenotypes
- Newly sequenced reads: xxx
- Assemblies: TBR
- Annotations : TBR
- Non redundant pangenome (75% identity threshold): TBR
- Presence/Absence matrix (1991 isolates) : TBR
- Variant calls relative to the K12 reference NC_000913.3 (https://www.ncbi.nlm.nih.gov/nuccore/556503834) for 1991 isolates : TBR
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Dr. Anne Farewell, University of Gothenburg, Department of Cell and Molecular Biology, Box 462, 405 30 Göteborg, Sweden +46317862583, +46317862599 (Fax), anne.farewell@cmb.gu.se
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Dr. Gianni Liti: University of Nice, Institute for Research on Cancer and Ageing of Nice (IRCAN), 28 Ave de Valombrose, 06107, Nice Cedex 02, France, +33 (0)4 93 37 7672, +33 (0)4 93 37 7676 (Fax), gianni.liti@unice.fr
- Dr. Matteo De Chiara: University of Nice, Institute for Research on Cancer and Ageing of Nice (IRCAN), 28 Ave de Valombrose, 06107, Nice Cedex 02, France, matteo.de-chiara@univ-cotedazur.fr
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Dr. Jonas Warringer: University of Gothenburg, Department of Chemistry and Molecular Biology, Associate Professor/Senior Lecturer, Box 462, 40530, Gothenburg, Sweden Phone: +46317863961, Fax: +46317862599, Jonas.warringer@cmb.gu.se
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Dr Danesh Moradigaravand, Centre for Computational Biology, Institute of Cancer and Genomic Sciences, Haworth Building (Y2), University of Birmingham, Edgbaston, Birmingham B15 2TTDr, +44 (0)121 414 8852, d.moradigaravand@bham.ac.uk
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Prof. Edward Moore: University of Gothenburg, Sahlgrenska Academy, Institute of, Biomedicine Box 440, 41346, Gothenburg, Sweden, +46 31 342 4696, +46 31 829 617 (Fax), edward.moore@gu.se
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Dr, Leopold Parts, Wellcome Trust, Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB101SA, United Kingdom, +441223 492375, +44 (0)1223 494919 (Fax), leopold.parts@sanger.ac.uk
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Prof. Jan Michiels: University of Leuven, Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, box 2460, B-3001 Heverlee, +32 16 32 9684, +32 16 32 19 63 (Fax), Jan.michiels@kuleuven.be
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Prof. Ville Mustonen, University of Helsinki, Department of Computer Science, Helsinki Institute for Information Technology, Institute of Biotechnology, PL 56 (Viikinkaari 9), 00014 Finland, +358503116206, +358294159602, v.mustonen@helsinki.fi
- Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) - https://www.jpiamr.eu/
- Centre for Antibiotic Resistance research in Gothenburg (CARe) - https://www.gu.se/care