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METAGENOMIC IDENTIFICATION OF THE DRIVERS OF THE ANTIMICROBIAL RESISTANCE TRANSMISSION ACROSS ONE HEALTH ECOSYSTEMS

Unité de recherche:  Anti-Infectieux : supports moléculaires des résistances et innovations thérapeutiques
Encadrement de la thèse: MARIE-CECILE PLOY marie-cecile.ploy@unilim.fr 
Financement du 01-10-2023 au 30-09-2026 origine Ministériel

Employeur: Université de Limoges
Start 1 octobre 2023
application deadline (23h59) 5 juin 2023

Project description

Antimicrobial resistance (AMR) in pathogens is a serious human health threat1. The emergence of AMR is driven by the sharing of resistance genes between bacteria from animals, humans, and the environment. Therefore, to curtail the emergence and spread of AMR, research, surveillance, and intervention strategies must integrate One Health approaches. In this context, the UMR INSERM 1092 uses the One Heath framework to explore the eco-evolutionary trajectories of AMR spread and to enhance surveillance systems.

The acquisition of AMR by pathogens is mainly due to the sharing of AMR plasmids, mobile genetic elements that can confer resistance to various antibiotics. Evidence points out that those plasmids have and are crossing ecological boundaries between humans, animals, and the environment while rapidly spreading worldwide. However, we still poorly understand the trajectories leading these plasmids to hop between environmental, animal, or human ecosystems and end up in deadly human pathogens.

This Ph. D. thesis aims to identify the ecological drivers of AMR transmission across a One Heath continuum. To address this objective, the candidate will use microbiology, molecular biology, and bioinformatic tools integrated within a metagenomic approach to identify key bacteria responsible for transferring AMR genes and plasmids across human, animal, and environmental habitats. Ultimately, the results from this Ph.D. will lead to the development of tools to support current One Health
surveillance systems of AMR and aid future development of strategies to slow the spread of antimicrobial resistance.

In parallel, the candidate will contribute to isolating some of the AR plasmids and bacteria and performing genomics analysis. More broadly, the candidate will be part of a dynamic and internationally recognized research group working on AMR. The UMR1092 has long-standing experience and expertise in applying the One Health approach, microbiology and molecular biology, and translational research to address AR.

Expected results

During this Ph.D, the candidate will have:
- Validated a metagenomic approach to determine the host of AMR genes and plasmids. Based on previously published methods called Hi-C10, molecular target
enrichment, and high throughput sequencing, the candidate will have designed an assay able to identify the bacteria carrying AMR genes and plasmids in
microbiomes.
- Identified the bacterial reservoirs of AMR plasmids across a One health continuum. Here the candidate will have carried out a sampling campaign across habitats
from the clinical, agricultural, and environmental ecosystems and use metagenomics, including the validated metagenomic approach, to identify the bacteria
carrying AMR genes and plasmids.
- Determined the bacteria driving AMR spread between habitats. In this last section, the candidate will have used a computational approach to identify whether certain
bacteria promote the transport of AMR genes and plasmids across.

Profile and skills required

Ideal candidates will:
- be curious and motivated,
- have a background in microbiology, molecular biology, and a good knowledge of bioinformatics,
- experience or strong motivation to learn programing language such as bash, R, and python,
- have good English communication for science.

Références bibliographiques

1. Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet 399, 629–655 (2022).
2. Holmes, A. H. et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 387, 176–187 (2016).
3. Pehrsson, E. C. et al. Interconnected microbiomes and resistomes in low-income human habitats. Nature 533, 212–216 (2016).
4. Larsson, D. G. J. & Flach, C.-F. Antibiotic resistance in the environment. Nat Rev Microbiol 20, 257–269 (2022).
5. Baquero, F., Coque, T. M., Martínez, J.-L., Aracil-Gisbert, S. & Lanza, V. F. Gene transmission in the One Health microbiosphere and the channels of antimicrobial resistance. Front. Microbiol. 10, (2019).
6. Forsberg, K. J. et al. The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107–1111 (2012).
7. Allen, H. K. et al. Call of the wild: Antibiotic resistance genes in natural environments. Nat. Rev. Microbiol. 8, 251–259 (2010).

8. Wang, R. et al. The global distribution and spread of the mobilized colistin resistance gene mcr-1. Nat Commun 9, 1179 (2018).
9. Weingarten, R. A. et al. Genomic analysis of hospital plumbing reveals diverse reservoir of bacterial plasmids conferring carbapenem resistance. mBio 9, (2018).
10. Stalder, T., Press, M. O., Sullivan, S., Liachko, I. & Top, E. M. Linking the resistome and plasmidome to the microbiome. ISME J 13, 2437–2446 (2019).

Co-direction : Stalder Thibault (UMR 1092)