Specific Targeting of Antimicrobial Resistant Strains in situ using Targeted-Antibacterial-Plasmids





Research Project: 2022-04-04 - 2025-03-04
Total sum awarded: €747 580

One health research programs are needed to tackle the problem of Antimicrobial Resistance (AMR), which is a major concern worldwide. The STARS-TAP innovative strategy is based on Targeted-Antibacterial-Plasmids (TAPs) that use DNA conjugation to deliver CRISPR/Cas systems exerting an antibacterial activity on specifically targeted multidrug-resistant (MDR) strains. In vitro, we have shown that TAPs can selectively kill MDR strains by targeting the chromosome or restore their susceptibility by targeting drug-resistance plasmids, without affecting non-targeted strains present in the bacterial population. Translating this in vitro proof of concept to various in situ settings would undoubtedly have a true impact by opening new intervention options to eliminate MDR strains from various ecosystems. Hence, we will develop a library of TAPs directed against a range of clinically and environmentally relevant MDR strains or against specific genes conferring resistance to expanded-spectrum beta-lactams and carbapenems. We will evaluate TAPs ability to specifically eliminate MDR strains or plasmids from the microbiotas associated with the animal gut or from hospital wastewater. We will also address TAPs dissemination and ability to eliminate AMR strains or plasmids from environmental soil or the plant rhizosphere. This unexplored and versatile antibacterial strategy could be a promising approach for preventive treatment of human and animals gut colonized with MDR strains, or even to avoid AMR spread within anthropized environmental reservoirs such as agricultural soils and wastewater.

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  • Christian Lesterlin, Centre National de la Recherche Scientifique (CNRS) – DR07, France (Coordinator)
  • Pierre Bogaerts, Katholieke Universiteit Leuven, Belgium (Partner)
  • Gregory Jubelin, INRAE, French National Institute for Agriculture, Food and Environment, France (Partner)
  • Anna Marzec-Grzadziel, Institute of Soil Science and Plant Cultivation – State Research Institute, Poland (Partner)
  • William Couet, INSERM, French National Institute of Health and Medical Research, France (Partner)

The global spread of antimicrobial resistance (AMR) among pathogenic bacteria is recognized as one of the biggest concerns in public health and a research priority in microbiology. Drug-resistance increases exponentially for certain bacterial organisms and is becoming the main threat to human health worldwide. As a consequence, national and international authorities have emphasized the need to taking a broad, coordinated approach to develop new antimicrobial strategies to fight against drug-resistant bacteria across multiple sectors such as human health and animal health, agriculture and environment1 (i.e. ‘One health’ major challenge). The STARS-TAP research program aims at developing an innovative non-antibiotic antibacterial methodology to specifically target AMR strains from natural bacterial communities in several ecosystems in situ. The proposed methodology is based on Targeted-Antibacterial-Plasmids (TAPs) that use DNA conjugation to deliver CRISPR/Cas systems exerting a strain-specific antibacterial activity. If successful, our research would represent a real breakthrough for clinical and environmental microbiology, and open new options for the elimination of AMR strains from various ecosystems. This unexplored and versatile strategy complementary to antibiotic treatments holds the potential to be used for curative or preventive decolonization purposes, or even in agriculture to tackle AMR prevalence in amended soils.