Modes of action of the methanol extract and 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid from Acacia polyacantha against multi-resistant Gram-negative bacteria

Background: Bacterial infections, especially those caused by multidrug-resistant (MDR) Gram-negative bacteria, remain a global health concern. Previous studies have reported the antibacterial activities of the methanol extract of the leaves of Acacia polyacantha Willd. (Fabaceae) (APL) as well as some of its phytoconstituents. In this study, APL and its constituent, 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid (GGOA) were evaluated on growth kinetics, bacterial membrane, and H+-ATPase proton pumps. The acute toxicity of APL was also studied. Methods: The effects of APL and GGOA on bacterial growth kinetics and the bacterial membrane was determined using spectrophotometric methods. Their effects on the bacterial H+-ATPase proton pumps were evaluated through the acidification of the bacterial external environment using a pH-meter. The acute toxicity of APL was determined using the standard limit test method described by the Organization for Economic Cooperation and Development (OECD) code 425. Results: APL and GGOA modified the bacterial kinetics of Providencia stuartii ATCC29916 with emphasis on the latent phase. They blocked the proton pumps of this bacterium and destroy the bacterial membrane. The medium lethal dose (LD50) of APL was greater than 5000 mg/kg body weight (b.w.). Conclusion: The results of the present study provide important and complementary information on APL and GGOA as good antibacterial candidates for combating infections due to MDR Gram-negative bacteria. Keywords: 3-O-[β-galactopyranosyl-(1→4)-β-D-galactopyranosyl]-oleanolic acid; Acacia polyacantha; acute toxicity; Gram-negative bacteria; mode of action; multidrug resistance.