N-acyl homoserine lactone quorum-sensing inhibitor acts as an antibiotic adjuvant to increase the susceptibility of Pseudomonas aeruginosa against β-lactam antibiotics

Pseudomonas aeruginosa is a Gram-negative bacterium and a major opportunistic pathogen that can cause extensive acute and chronic infections. β-lactam antibiotics are the most commonly used prescription antibiotics worldwide and play a crucial role in the treatment of Pseudomonas aeruginosa infections. However, antibiotic resistance (AMR) is a global challenge. The β-lactam resistance in Gram-negative bacteria is due to the production of β-lactamases, including extended-spectrum β-lactamases, metallo-β-lactamases, and carbapenem-hydrolyzing class D β-lactamases. To restore the efficacy of this type of antibiotic, the most effective strategy is to combine it with β-lactamase inhibitors (BLI). In this study, we were pleasantly surprised to find that the quorum sensing inhibitor 2-(4-bromophenyl)-N-(2-oxotetrapyridinefuran-3-yl) butanamide (compound No.10) of Pseudomonas aeruginosa, when combined with β -lactam antibiotics, not only could inhibit the formation of biofilms in the standard and clinical strains of Pseudomonas aeruginosa, but also promoted the entry of antibiotics into the bacteria to exert their bactericidal effects. Moreover, it can also inhibit the expression of the drug resistance gene ampc in Pseudomonas aeruginosa, thereby suppressing the degradation effect of β-lactamase on β-lactam antibiotics.