Published on December 14, 2018 | Updated on December 14, 2018


Shifting perspective on antibiotic resistance: is resistance propagation driven by the selfish competing traits of mobile genetic elements?

Coordinator :Xavier Charpentier (CIRI) - Ecofect partners : Samuel Venner (LBBE), Maria-Halima Laaberki (CIRI) &Tristan Ferry (CIRI/HCL) - External partners : Marisa Haenni (Anses-Lyon) & Christine Gaspin (INRA)

Antibiotic resistance is a global concern that hampers the control of infectious diseases and increases the cost of health care. New mechanisms of antibiotic resistance regularly emerge and some spread globally, yet our understanding of this phenomenon is limited. A leading contributing factor to the spread of antibiotic resistance is horizontal gene transfer (HGT) of mobile genetic elements (MGE) through which pathogens can acquire antibiotic resistance genes (ARG) from other bacteria. The MGE carrying ARG (AR-MGE) are widespread and strongly vary in their gene composition. Distinct AR-MGE can therefore be considered as entities competing to exploit bacteria, considered here as their limiting resource.
In this project, we therefore formulate the hypothesis that the AR-MGE should arbor selfish intrinsic properties (hereafter called “selfish competing traits”) aiming at maximizing their propagation in this context of competition between AR-MGE. Based both on solid data from the literature and preliminary results, we hypothesize that one of the potential major competing traits of AR-MGE correspond to their ability, following their insertion, to decrease the rate of acquisition of new MGE, through HGT, by the recipient bacterium. In this way, AR-MGE could reduce opportunities of spread of “competitor” MGE, and increase their own chances of invasion and/or persistence in bacterial communities in specific ecological context. In addition, we hypothesize that under massive and persistent antibiotic treatment, competing traits could drastically accelerate the process of adapted AR-MGE invasion and spread within bacterial communities. This could profoundly influence interactions between bacterial species, and can lead to community instability, and even dysbiosis in the case of microbiota.
The general objective of the project is to accumulate experimental and theoretical evidence to determine (i) whether AR-MGEs behave as competing entities (minimizing propagation of other AR-MGEs), (ii) whether their competing traits generate intra-genomic conflict (between MGE and other bacterial genes), and (iii) whether selfish competing traits modify dramatically the emergence and spreading of antibiotic-resistance within bacterial communities, as well as their stability and resilience. Our project aims therefore to establish a new paradigm in the dynamics of antibiotic resistance based on the evolutionary theory of the “selfish gene” within the context of competing AR-MGE in bacterial communites, by combining theoretical and empirical approaches.

Coordinator : Xavier Charpentier, team "Transfert de Gène Horizontal chez les Bactéries Pathogènes" (CIRI)
Ecofect partners :  Samuel Venner, team "Ecologie Quantitative et Evolutive des Communautés" (LBBE),  Maria-Halima Laaberki, team "Transfert de Gène Horizontal chez les Bactéries Pathogènes" (CIRI), and Tristan Ferry, team "Pathogénie des Staphylocoques" (CIRI).
External partners : Marisa Haenni (ANSES Lyon) and Christine Gaspin (INRA Toulouse).
Project duration : 3 years
Financing :
PhD & research engineer fellowships plus consumable money
PhD fellows: Anne-Sophie Godeux, Tony Rochegüe
Research engineer:
Gabriel Carvalho