Acacia senegal Budmunchiamines as a Potential Adjuvant for Rejuvenating Phenicol Activities towards Escherichia coli-Resistant Strains

The continuous emergence of bacterial resistance alters the activities of different antibiotic families and requires appropriate strategies to solve therapeutic impasses. Medicinal plants are an attractive source for researching alternative and original therapeutic molecules. In this study, the fractionation of natural extracts from A. senegal and the determination of antibacterial activities are associated with molecular networking and tandem mass spectrometry (MS/MS) data used to characterize active molecule(s). The activities of the combinations, which included various fractions plus an antibiotic, were investigated using the chessboard test. Bio-guided fractionation allowed the authors to obtain individually active or synergistic fractions with chloramphenicol activity. An LC-MS/MS analysis of the fraction of interest and molecular array reorganization showed that most identified compounds are Budmunchiamines (macrocyclic alkaloids). This study describes an interesting source of bioactive secondary metabolites structurally related to Budmunchiamines that are able to rejuvenate a significant chloramphenicol activity in strains that produce an AcrB efflux pump. They will pave the way for researching new active molecules for restoring the activity of antibiotics that are substrates of efflux pumps in enterobacterial-resistant strains.

Automated summary

The emergence of bacterial resistance has changed the effectiveness of different antibiotic families, and research into alternative therapeutic molecules from medicinal plants is needed. This study used molecular networking and MS/MS data to characterize active molecules in natural extracts from A. senegal. The activities of different combinations of fractions and antibiotics were tested using the chessboard test. Bio-guided fractionation identified fractions with chloramphenicol activity, and LC-MS/MS analysis revealed that these fractions contained Budmunchiamines, which are macrocyclic alkaloids. This study provides a potential source of bioactive secondary metabolites related to Budmunchiamines that can restore chloramphenicol activity in enterobacterial-resistant strains with AcrB efflux pumps.