Botanical from the bark of Zizyphus jujuba Mill. (Rhamnaceae) had weak anti-Klebsiella activity, but strongly potentiated the effects of antibiotics against multidrug-resistant phenotypes

Abstract

Background: Klebsiella pneumoniae is medically the most important species of this genus. Klebsiella oxytoca also cause infections in human but to a much lesser degree than K. pneumoniae. In this work, the antibacterial potential of the methanol extract from the bark of Zizyphus jujuba (ZJB) was evaluated against the multidrug-resistant (MDR) clinical isolates of Klebsiella pneumoniae and Klebsiella oxytoca overexpressing AcrAB-TolC efflux pumps.

Methods: The broth microdilution method combined with the rapid para-iodonitrotetrazolium chloride (INT) colorimetric technique was used to determine the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of ZJB alone, in the presence of an efflux pump inhibitor (EPI) phenylalanine-arginine β-naphthylamide (PAβN), or in the presence of antibiotics. The phytochemical screening of ZJB was evaluated using standard methods.

Results: ZJB displayed weak antibacterial activities with MIC values above 625 μg/mL in all the 14 tested Klebsiella species. In the presence of PAβN, the activity of ZJB increased by 4- to more than 128-fold on all the tested bacteria. At MIC/2 and MIC/4, ZJB potentiated the activity of doxycycline (DOX), levofloxacin (LEV), imipenem (IMI), ciprofloxacin (CIP), ceftriaxone (CRO), and tetracycline (TET) against at least 80% of the MDR bacterial strains tested. ZJB contains alkaloids, flavonoids, triterpenes, saponins, phenols, and anthocyanins.

Conclusion: This study has demonstrated that ZJB could be used as an antibacterial agent if it is combined with an efflux pump inhibitor or with antibiotics against MDR bacteria over-expressing active efflux pumps.