Tushar Khare1, Sneha Mahalunkar2, Varsha Shriram3, Suresh Gosavi4, Vinay Kumar5. 1. Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University), Ganeshkhind, Pune, 411016, India; Department of Environmental Science, Savitribai Phule Pune University, Pune, 411007, India. 2. School of Basic Medical Science, Savitribai Phule Pune University, Pune, 411007, India. 3. Department of Botany, Prof. Ramkrishna More Arts, Commerce and Science College (Savitribai Phule Pune University), Pune, 411044, India. 4. School of Basic Medical Science, Savitribai Phule Pune University, Pune, 411007, India; Department of Physics, Savitribai Phule Pune University, Pune, 411007, India. Electronic address: swg@physics.unipune.ac.in. 5. Department of Biotechnology, Modern College of Arts, Science and Commerce (Savitribai Phule Pune University), Ganeshkhind, Pune, 411016, India; Department of Environmental Science, Savitribai Phule Pune University, Pune, 411007, India. Electronic address: vinaymalik123@gmail.com.
Abstract
A global upsurge in emergence and spread of antibiotic resistance (ABR) in bacterial populations is a serious threat for human health. Unfortunately, ABR is no longer confined to nosocomial environments and is frequently reported from community microbes as well. The ABR is resulting in shrinking potent antibiotics pool and thus necessitating novel and alternative therapies and therapeutics. Current investigation was aimed to assess the synergistic potential of a synthesized, phytomolecule-loaded, polysaccharide-stabilized metallic nanoparticles (NPs) against Pseudomonas aeruginosa (PA) and Escherichia coli (EC) isolated from river waters. ABR profiling of these strains characterized them as multidrug resistant (MDR). Synthesized embelin (Emb, isolated from Embelia tsjeriam-cottam)-loaded, chitosan-gold (Emb-Chi-Au) NPs were assessed for their potential synergistic activity with ciprofloxacin (CIP) via checker-board assay and time-kill curve analysis. The NPs reduced the minimal inhibitory concentration (MIC) of CIP by 16- and 4-fold against MDR PA (PA-r) and EC (EC-r) strains, respectively. Fractional inhibitory concentration (FIC) indices with ≤0.5 values confirmed the synergy between the Emb-Chi-Au NPs and CIP, which was further confirmed at ½ MICs in both PA-r and EC-r via time-kill curve analysis. In order to decipher the mode of action, efflux pump inhibitory effects of Emb-Chi-Au NPs were evaluated in terms of the increase in the EtBr mediated fluorescence in control versus NP-treated MDR strains. Molecular docking based in silico simulations were used to predict the interactions between Emb and the active sites of the efflux pump related proteins in PA-r (MexA, MexB and OprM) and EC-r (AcrA, AcrB and TolC), which revealed the probable bond formation between Emb and respective amino acid residues.
A global upsurge in emergence and spread of antibiotic resistance (ABR) in bacterial populations is a serious threat for human health. Unfortunately, ABR is no longer confined to nosocomial environments and is frequently reported from community microbes as well. The ABR is resulting in shrinking potent antibiotics pool and thus necessitating novel and alternative therapies and therapeutics. Current investigation was aimed to assess the synergistic potential of a synthesized, phytomolecule-loaded, pan class="Chemical">polysaccharide-stabilized metallic nanoparticles (NPs) against Pseudomonas aeruginosa (PA) and Escherichia coli (EC) isolated from river waters. ABR profiling of these strains characterized them as multidrug resistant (MDR). Synthesized embelin (Emb, isolated from Embelia tsjeriam-cottam)-loaded, chitosan-gold (Emb-Chi-Au) NPs were assessed for their potential synergistic activity with ciprofloxacin (CIP) via checker-board assay and time-kill curve analysis. The NPs reduced the minimal inhibitory concentration (MIC) of CIP by 16- and 4-fold against MDR PA (PA-r) and EC (EC-r) strains, respectively. Fractional inhibitory concentration (FIC) indices with ≤0.5 values confirmed the synergy between the Emb-Chi-Au NPs and CIP, which was further confirmed at ½ MICs in both PA-r and EC-r via time-kill curve analysis. In order to decipher the mode of action, efflux pump inhibitory effects of Emb-Chi-Au NPs were evaluated in terms of the increase in the EtBr mediated fluorescence in control versus NP-treated MDR strains. Molecular docking based in silico simulations were used to predict the interactions between Emb and the active sites of the efflux pump related proteins in PA-r (MexA, MexB and OprM) and EC-r (AcrA, AcrB and TolC), which revealed the probable bond formation between Emb and respective amino acid residues.
Authors: Amr Selim Abu Lila; Bader Huwaimel; Ahmed Alobaida; Talib Hussain; Zeeshan Rafi; Khalid Mehmood; Marwa H Abdallah; Turki Al Hagbani; Syed Mohd Danish Rizvi; Afrasim Moin; Abobakr F Ahmed Journal: Materials (Basel) Date: 2022-08-18 Impact factor: 3.748