Unveiling the anti-Klebsiella activity of methanol extracts from Hallea ciliata leaves and barks against multidrug-resistant strains overexpressing AcrAB-TolC efflux pumps

Background: Infectious diseases are considered one of the most critical threats to public health. The present work aimed to determine the anti-Klebsiella activity of methanol extracts (botanicals) of Hallea ciliata leaves (HCL) and bark (HCB) against multidrug-resistant phenotypes over-expressing ACrAB-TolC efflux pumps. Methods: The antibacterial activity of botanicals alone and in combination with PAβN and antibiotics, was determined using the broth microdilution method. The effects of HCL on H+/ATPases and the qualitative phytochemical screening were assessed using standard experimental protocols. Results: The results indicate that HCL and HCB had antibacterial activity against 75% and 56.25% of the tested bacterial strains, with minimum inhibitory concentrations (MIC) ranging from 64 to 1024 µg/mL and from 64 to 512 µg/mL, respectively. They showed strong activity against Klebsiella oxytoca KO107 and Klebsiella pneumoniae K2 with MICs of 64 µg/mL for HCL and HCB, respectively. When the functioning of proton pump dysfunction was assessed in the presence of HCL, it was observed to affect Klebsiella oxytoca KO107. Furthermore, when combined with PAβN, the botanicals demonstrated improved activity against 100% of the tested strains and isolates, with the activity improvement factor (AIF) ranging from 2 to 256. Additionally, the study found that the botanicals enhanced the activity of certain antibiotics at MIC/2 and MIC/4, including ampicillin, penicillin, and ciprofloxacin. Phytochemical screening of the botanicals revealed the presence of alkaloids, triterpenes, phenols, flavonoids, saponins, and anthocyanins. Conclusion: Overall, HCL and HCB are sources of antibacterial substances that could be valuable in combating multidrug-resistant (MDR) bacteria from the Klebsiella genus that over-express efflux pumps.