Plasmid curing by an Ethiopian barley: a natural feed/food approach to reduce plasmid mediated antibiotic resistance

Bacterial plasmids are genetic elements that may carry antimicrobial resistance genes, which can be exchanged between bacteria, acting as "messengers" and thus contributing to the emergence of multidrug-resistant bacteria. The main objective of this project was to evaluate the potential of Ethiopian barley (Hordeum spontaneum) to eliminate plasmid-carrying genes that determine antimicrobial resistance.

The first step was developing an in vitro test to evaluate the effect of the gross extract and fractions of the Ethiopian barley on the inactivation of plasmids in bacterial strains (reference and wild strains). The second step was to design an in vivo test combining an experimental murine infection and the evaluation, using metagenomics tools, of the effect of the gross extract and barley fractions treatment

In vitro assays showed that bacterial growth was not modified by exposure to the Ethiopian barley, regardless of the presence or absence of an antibiotic. This initial evaluation showed that, under the experimental conditions and concentrations used, the Ethiopian barley extract could not induce a significant reduction of resistance plasmids. On the other hand, the decrease of bacterial population and increase of inhibition antimicrobials halos after exposure to the extract in some strains suggests a possible metabolic interference, with increased permeability in particular cephalosporins and carbapenems, or even the modulation of beta-lactamases expression. by the plasmids.

The project's innovation is grounded in the strategy of "kill the messenger, not the bacteria" to address the increasing antibiotic resistance problem.

From a One Health perspective, the project proposed a complementary approach to extend the lifespan of new antimicrobials and the potential of existing animal and human therapies through the elimination of plasmids carrying resistance genes, thus attacking one of the mechanisms involved in the process of antimicrobial resistance. The reduction of antimicrobial resistance in bacteria of animal origin and in their habitat could significantly contribute to the current antimicrobial load. Not only is the direct contribution (less resistant bacteria released into the environment), but also the possibility of a new therapeutic tool.

Some of the following steps foreseen is the evaluation of the extract concentration with healing potential in other bacterial populations, diversifying the action of the extract in different classes of antimicrobials, determining the healing capacity in other species, plasmid types, and resistance markers and to identify the fraction of barley extract using chromatographic techniques.