Journal of global antimicrobial resistance · 2025
Investigating the adjuvant activity of the proline-rich antimicrobial lipopeptide C12-PRP against antimicrobial-resistant veterinary bacterial isolates.
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Deo Soumya, Sharoze Aimeen, Esenbekova Meerim, White Dawn, Schweizer Frank, Mani Ramesh Kumar, Gorityala Bala Kishan, Kumar Ayush
Аннотация
OBJECTIVES: Farm animals exposed to excessive amounts of antibiotics are reservoirs for antimicrobial-resistance genes and multidrug-resistant bacteria. The goal of this study was to investigate the adjuvant activity of a previously synthesized, proline-rich lipopeptide called C12-PRP in combination with various antibiotics against multidrug-resistant E. coli isolated from chicken and cattle.
METHODS: The microbroth dilution method was used to determine the minimum inhibitory concentration of 10 antibiotics against four E. coli isolates. The adjuvant activity of C12-PRP was then tested in combination with the same antibiotics using a checkerboard assay. The best synergistic antibiotic-C12-PRP combinations were tested with the most resistant E. coli isolate using the Galleria mellonella insect infection model. A fluorescence-based membrane permeabilization assay was used to investigate a possible mode of action for C12-PRP.
RESULTS: The four E. coli isolates showed varying resistance to the antibiotics (0.008 µg/mL to ≥256 µg/mL), and overall, the addition of C12-PRP lowered the minimum inhibitory concentration. The two most-potent antibiotic-C12-PRP combinations were with novobiocin and erythromycin showing a susceptibility increase of 128-fold and up to 32-fold, respectively. G. mellonella survival was significantly improved when C12-PRP was included with novobiocin or erythromycin during treatment of infected larvae. Membrane permeabilization of an E. coli isolate was markedly higher in the presence of C12-PRP.
CONCLUSIONS: We demonstrated the synergistic ability of C12-PRP to enhance antibiotic activity and reduce the virulence of the veterinary E. coli isolates, strengthening the potential promise of this adjuvant candidate as a therapeutic agent for multidrug-resistant bacteria.
METHODS: The microbroth dilution method was used to determine the minimum inhibitory concentration of 10 antibiotics against four E. coli isolates. The adjuvant activity of C12-PRP was then tested in combination with the same antibiotics using a checkerboard assay. The best synergistic antibiotic-C12-PRP combinations were tested with the most resistant E. coli isolate using the Galleria mellonella insect infection model. A fluorescence-based membrane permeabilization assay was used to investigate a possible mode of action for C12-PRP.
RESULTS: The four E. coli isolates showed varying resistance to the antibiotics (0.008 µg/mL to ≥256 µg/mL), and overall, the addition of C12-PRP lowered the minimum inhibitory concentration. The two most-potent antibiotic-C12-PRP combinations were with novobiocin and erythromycin showing a susceptibility increase of 128-fold and up to 32-fold, respectively. G. mellonella survival was significantly improved when C12-PRP was included with novobiocin or erythromycin during treatment of infected larvae. Membrane permeabilization of an E. coli isolate was markedly higher in the presence of C12-PRP.
CONCLUSIONS: We demonstrated the synergistic ability of C12-PRP to enhance antibiotic activity and reduce the virulence of the veterinary E. coli isolates, strengthening the potential promise of this adjuvant candidate as a therapeutic agent for multidrug-resistant bacteria.