Abstract
The number of fully active antibiotic options that treat nosocomial infections due to multidrug-resistant Acinetobacter baumannii (A. baumannii) is extremely limited. Magnolia officinalis, Mahonia bealei, Rabdosia rubescens, Rosa rugosa, Rubus chingii, Scutellaria baicalensis, and Terminalia chebula plant extracts were previously shown to have growth inhibitory activity against a multidrug-resistant clinical strain of A. baumannii. In this study, the compounds responsible for their antimicrobial activity were identified by fractionating each plant extract using high performance liquid chromatography, and determining the antimicrobial activity of each fraction against A. baumannii. The chemical structures of the fractions inhibiting >40% of the bacterial growth were elucidated by liquid chromatography/mass spectrometry analysis and nuclear magnetic resonance spectroscopy. The six most active compounds were identified as: ellagic acid in Rosa rugosa; norwogonin in Scutellaria baicalensis; and chebulagic acid, chebulinic acid, corilagin, and terchebulin in Terminalia chebula. The most potent compound was identified as norwogonin with a minimum inhibitory concentration of 128 µg/mL, and minimum bactericidal concentration of 256 µg/mL against clinically relevant strains of A. baumannii. Combination studies of norwogonin with ten anti-Gram negative bacterial agents demonstrated that norwogonin did not enhance the antimicrobial activity of the synthetic antibiotics chosen for this study. In conclusion, of all identified antimicrobial compounds, norwogonin was the most potent against multidrug-resistant A. baumannii strains. Further studies are warranted to ascertain the prophylactic and therapeutic potential of norwogonin for infections due to multidrug-resistant A. baumannii.
Highlights
Outbreaks of infections due to Acinetobacter baumannii (A. baumannii) have been reported worldwide [1], and have been attributed to contamination of inanimate objects in the hospital setting and facilitated by healthcare workers who may transmit this organism via direct person-to-person contact [2,3]
The strains belonged to different clones based on repetitive-polymerase chain reaction amplification, and their dendrogram is shown in Figure S1 [9]. 31P was determined to be resistant to piperacillin/tazobactam, anti-pseudomonal cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones by VITEKH2; and sensitive to colistin by Etest based on interpretations according to Clinical and Laboratory Standards Institute (CLSI) breakpoints [10]
Dry powders of the plant extracts were obtained as follows: Magnolia officinalis, Rubus chingii, Scutellaria baicalensis and Terminalia chebula were obtained from Sun Ten Laboratories, Inc. (Irvine, California, USA); those of Mahonia bealei and Rosa rugosa were obtained from Bio Essence Corporation (Richmond, California, USA); and those of Rabdosia rubescens were obtained from Mayway Corporation (Torrance, California, USA)
Summary
Outbreaks of infections due to Acinetobacter baumannii (A. baumannii) have been reported worldwide [1], and have been attributed to contamination of inanimate objects in the hospital setting and facilitated by healthcare workers who may transmit this organism via direct person-to-person contact [2,3]. Fully active antibiotic options available to treat nosocomial infections due to multidrug-resistant (MDR) A. baumannii are extremely limited [1]. In order to identify novel treatment options, commercially available plant extracts were previously screened for their ability to inhibit MDR A. baumannii in vitro. Flavones, and phenolic compounds are reported to have low to moderate inhibitory effects on A. baumannii in vitro [5,6]. We hypothesized that the anti-MDR A. baumannii activity of these plant extracts may result from the combination of tannins and non-tannins that may be present in the extracts. We identified active chemical compounds in the anti-MDR A. baumannii plant extracts and characterized their antimicrobial properties in vitro
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