title: Augmenting the potency of third-line antibiotics with Berberis aristata: In vitro synergistic activity against carbapenem-resistant Escherichia coli.
abstract: The aim of this study was to analyse the in vitro synergistic antibacterial potential of an aquoethanolic extract of the stem bark of Berberis aristata (PTRC-2111-A) with third-line antibiotics against carbapenem-resistant Escherichia coli. PTRC-2111-A was prepared and was characterised using phytochemical- and bioactivity-based fingerprinting. Fourier transform infrared spectroscopy (FTIR) and liquid chromatography-mass spectrometry (LC-MS) analyses were performed, and superoxide and hydroxyl scavenging activities were assessed in conjunction with in vitro antimicrobial efficacy testing against the test micro-organism. Analysis of drug combinations of PTRC-2111-A and third-line antibiotics was performed using CompuSyn software. PTRC-2111-A from B. aristata was found to have seven common functional groups in comparison with the pre-identified marker compound quercetin, and phytochemical quantitation analysis revealed the presence of 25.44% alkaloids. Moreover, PTRC-2111-A was found to contain isoquinoline alkaloids, namely berbamine, berberine, reticuline, jatrorrhizine, palmatine and piperazine, as elucidated in the LC-MS analysis. Analysis of combinations of PTRC -2111-A and antibiotics revealed synergistic behaviour [fractional inhibitory concentration index (FICI)<1] with colistin, tigecycline and amoxicillin/clavulanate potassium (Augmentin(®)), whereas antagonism (FICI>1) was seen with ertapenem and meropenem.
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi 110054, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Thakur
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi 110054, India. Electronic address: ptrcmanuscripts@gmail.com.
authors.forename: Raman
authors.initials: R
authors.lastname: Chawla
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi 110054, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Goel
authors.affiliation: Department of Biotechnology, Jamia Hamdard, New Delhi 110062, India.
authors.forename: Alka
authors.initials: A
authors.lastname: Narula
authors.affiliation: Office of DG (LS), Defence Research and Development Organisation, DRDO Bhawan, New Delhi, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Arora
authors.affiliation: Division of CBRN Defence, Institute of Nuclear Medicine and Allied Sciences (INMAS), New Delhi 110054, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Sharma
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D028142:Berberis / Q000737:chemistry*; D015780:Carbapenems; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D010936:Plant Extracts
keywords: Berberis aristata; Escherichia coli; Fractional inhibitory concentration index; Multidrug resistance; New Delhi metallo-β-lactamase-1 (NDM-1); Synergistic effects