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.

Toxicity and bacterial anti-motility activities of the hydroethanolic extract of Acacia senegal (L.) Willd (Fabaceae) leaves.

BACKGROUND: Acacia senegal is a plant traditionally used for its various properties, including the treatment of infectious diseases. Recently, our team has demonstrated the ability of the hydroethanolic extract of the leaves to increase the activity of phenicol antibiotics against multi-resistant bacteria. The aim of this work is to determine the toxicological effects of the extract and its capacity to inhibit the bacterial mobility of Gram-negative bacteria, in order to evaluate the level of safety use of this plant. METHODS: The cytotoxicity test was performed using the neutral red absorption method. Acute and sub-acute oral toxicity were conducted on NMRI mice and Wistar rats. The behaviour and adverse effects were recorded during the 14 days of the acute study. For the subacute test, biochemical parameters, food and water consumption, and morphological parameters were determined. The anti-motility activities were evaluated on Pseudomonas aeruginosa PA01 and Escherichia coli AG100, using specific concentrations of Agar as required by the method. RESULTS: HEASG induced inhibition of keratinocytes cell growth with an IC50 of 1302 ± 60 µg/mL. For the acute toxicity study in mice, the single dose of extract of 2000 mg/kg body weight caused no deaths and no behavioural changes were observed; therefore, the median lethal dose (LD50) of HEASG was calculated to 5000 mg/kg body weight. In Wistar rats, no mortality was observed at 250, 500 and 1000 mg/kg/day during the 28-day subacute oral toxicity study. The weights of both females and males increased globally over time, regardless of the batch. No statistically significant differences were registered for organ weights and biochemical parameters, except for chloride for biochemical parameters. Water and food consumption did not change significantly. Furthermore, no macroscopic changes in organ appearance were observed. Regarding anti-motility activity, the extract has reduced the swarming motility of PA01 and AG100 significantly at the concentration of 32 µg/mL (P < 0.001). The extract has reduced the swimming motility (P < 0.01) of PA01 but not AG100. CONCLUSIONS: The results suggest that hydroethanolic extract of A. senegal leaves has significant activity against bacterial motility and relatively low toxicity.

Acacia senegal Extract Rejuvenates the Activity of Phenicols on Selected Enterobacteriaceae Multi Drug Resistant Strains.

This study reported the phytochemical composition of two hydroethanolic extracts of Acacia senegal and Acacia seyal trees from Burkina Faso and their activities, alone or in combination with selected antibiotics, against multidrug resistant bacteria. High performance thin layer chromatography (HPTLC) method was used for phytochemical screening. Total phenolic and total flavonoid ant tannins in leaves extracts contents were assessed by spectrophotometric method. The minimal inhibitory concentrations (MICs) of plant extracts and antibiotics were determined using the microdilution method and p-iodonitrotetrazolium chloride. Combinations of extracts and antibiotics were studied using checkerboard assays. Screening revealed the presence of phenolic compounds, flavonoids, and tannins in the hydroethanolic extract (HE) of the leaves. The HE of A. seyal showed the highest total phenolic (571.30 ± 6.97 mg GAE/g), total flavonoids (140.41 ± 4.01 mg RTE/g), and tannins (24.72 ± 0.14%, condensed; 35.77 ± 0.19%, hydrolysable tannins). However, the HE of A. senegal showed the lowest total phenolic (69.84 ± 3.54 mg GAE/g), total flavonoids (27.32 ± 0.57 mg RTE/g), and tannins (14.60 ± 0.01%, condensed; 3.09 ± 0.02%, hydrolysable). The MICs for HE and antibiotics were in the range of 2-512 and 0.008-1024 mg/L, respectively. All tested HE presented an MIC greater than 512 mg/L except HE of A. senegal. The lowest MIC value (128 mg/L) was obtained with HE of A. senegal against Klebsiella aerogenes EA298 and Escherichia coli AG100A. Interesting restoring effects on chloramphenicol and florphenicol activity were detected with alcoholic extracts of A. senegal against resistant E. coli and K. aerogenes strains that overproduce AcrAB or FloR pumps. The adjuvant effect of HE of A. senegal suggests that the crude extract of leaves could be a potential source of molecules for improving the susceptibility of bacteria to phenicols antibiotics.