Antibiotic resistance has become a major issue in public health especially for one of the most used antibiotics; the third-generation cephalosporins. one of the main resistance mechanisms in Enterobacteriaceae, is the production of extended-Spectrum β-lactamases. Here, we demonstrated that the oligonucleotide therapy is an efficient approach to reduce the resistance of bacteria to antibiotic treatment. Lipid oligonucleotides (LONs) were proved to be efficient strategies in both delivering the oligonucleotide sequences in the prokaryotic cells and decreasing the Minimum inhibitory concentration of resistant bacteria to a third generation cephalosporin, the ceftriaxone. Accordingly, we demonstrated the strong antimicrobial potential of this Lon strategy targeting the ß-lactamase activity on both clinical and laboratory strains. our results support the concept that the self-delivery of oligonucleotide sequences via lipid conjugation may be extended to other antimicrobial drugs, which opens novel ways to struggle against the antibiotic resistance.
Our experimental data demonstrate for the first time, to our knowledge, the mobilization of a β-lactamase gene mediated by a member of the IS91 family and highlight the important role of this mobile genetic element in the spread of antibiotic resistance genes.
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