Inhibition of New Delhi Metallo-β-Lactamase 1 (NDM-1) Producing Escherichia coli IR-6 by Selected Plant Extracts and Their Synergistic Actions with Antibiotics

Abstract

Improper use of antibiotics has led to a great concern in the development of pathogenic microbial resistance. New Delhi metallo-β-lactamase 1 (NDM-1) producing bacteria are resistant to most of the β-lactam antibiotics, and so far, no new compounds have been clinically tested against these bacteria. In this study, ethanol extracts from the leaves of 240 medicinal plant species were screened for antibacterial activity against an NDM-1 Escherichia coli strain. The extracts that showed antibacterial activity were then tested for minimum inhibitory concentrations (MICs) and zones of inhibition. The extract from Combretum albidum G. Don, Hibiscus acetosella Welw. ex Hiern, Hibiscus cannabinus L., Hibiscus furcatus Willd., Punica granatum L., and Tamarindus indica L. showed bactericidal activity between 5 and 15 mg/ml and the MIC was between 2.56 and 5.12 mg/ml. All six plant extracts inhibited activity of the NDM-1 enzyme in vitro, and the IC50 value ranged between 0.50 and 1.2 ng/μl. Disruption of bacterial cell wall integrity by the plant extracts was clearly visible with scanning electron microscopy. Increases in membrane permeability caused 79.4–89.7% bacterial cell deaths as investigated by fluorescence-activated cell sorting. All the plant extracts showed synergistic effects when combined with colistin [fractional inhibitory concentration (ΣFIC) = 0.125–0.375], meropenem (ΣFIC = 0.09–0.313), and tetracycline (ΣFIC = 0.125–0.313). Thus, the plant extracts can be fractionated for the identification of active compounds, which could be used as new antibacterial compounds for the development of drugs against NDM-1 E. coli in addition to their use in combination therapy.

NDM Metallo-β-Lactamases and Their Bacterial Producers in Health Care Settings

“…The extracts from Combretum albidum G. Don, Hibiscus acetosella Welw. ex Hiern, Hibiscus cannabinus L., Hibiscus furcatus Willd., Punica granatum L., and Tamarindus indica L. inhibited the NDM-1 enzyme in vitro and showed synergistic effects when combined with colistin (312). In another study, magnolol, from the bark of magnolia trees, significantly inhibited NDM-1 enzyme activity and was able to restore the activity of meropenem against NDM-positive E. coli (28).…”

“…Plant derivatives. In one particular study of note, ethanol extracts from the leaves of 240 medicinal plant species were screened for antibacterial activity (312). The extracts from Combretum albidum G. Don, Hibiscus acetosella Welw.…”

Phytochemical Study and Antibacterial and Antibiotic Modulation Activity of Punica granatum (Pomegranate) Leaves

“…e work [30] showed that pomegranate ethanol extract inhibited recombinant New Delhi metallo-β-lactamase 1 (NDM-1) activity and the IC 50 value was 0.76 ng/μL. e same extract caused an increase in NDM-1 E. coli cell permeability.…”

Zoonotic Diseases and Phytochemical Medicines for Microbial Infections in Veterinary Science: Current State and Future Perspective

“…Nonetheless, the mechanisms of action of most phytotherapeutic chemicals are not fully understood. However, their synergistic antimicrobial activity is generally assumed to damage the bacterial membrane by lipophilic compounds or reduce cell division by DNA synthesis inhibition ( 8 ).…”

“…Phytotherapy has become an important new concept in healthcare research that was prompted by the need for alternatives to ineffective conventional antibiotics. The development of novel and efficient extraction techniques has led to renewed and increasing interest in plant-derived bioactive compounds ( 8 ). Examples of phytotherapeutic drugs include oleanolic acid, which is used as a natural adjuvant for aminoglycosides as it increases their membrane permeability ( 9 ).…”