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      https://www.ias.ac.in/article/fulltext/jbsc/045/0147

    • Keywords

       

      Bactericidal; drug-resistance bacteria; liposomal models; mitocurcumin; new structural class antibiotics; pharmacological properties; time-kill assay

    • Abstract

       

      Many pathogenic species of bacteria are showing increasing drug resistance against clinically used antibiotics. Molecules structurally distant from known antibiotics and possessing membrane targeting bactericidal activities are more likely to display activity against drug-resistant pathogens. Mitocurcumin (MitoC) is one of such compounds, synthesized by triphenyl-phosphonium conjugation with curcumin, and has been shown recently from our laboratory to have broad-spectrum bactericidal activity (Kumari et al. Free Radic. Biol. Med. 143 140–145). Here, we further demonstrate the antibacterial properties of MitoC against resistant strains and also its mechanism of action. It displays efficient bactericidal activity against multidrug-resistant Staphylococcus aureus and Streptococcus pneumoniae (MIC values in the 1.5–12.5 µM range), and coagulase-negative Staphylococci do not show resistance development against MitoC. Liposome based studies and MIC values against TolC deletion mutant (ΔtolC; outer membrane protein) of E. coli suggest extensive membrane damage to be the primary mechanism of bactericidal activity.MitoC did not exhibit toxicity in BALB/c mice with an oral administration of 250 mg/kg body weight and was found to be totally safe without any significant effect on haematological, biochemical parameters and inflammatory responses. Its rapid bactericidal action as assessed by in vitro time-kill assay against B. subtilis, compared to ciprofloxacin, and long half-life in rodent serum, suggest that MitoC could be an excellent lead-molecule against drug-resistant pathogens.The highlights of the study are that mitocurcumin belongs to a structurally new class of bactericidal compounds. It displays activity against MDR strains of pathogenic bacteria and challenging MRSA. Liposome-based studies confirm the membrane damaging property of the molecule. Mitocurcumin does not show resistance development even after 27 bacterial generations.

    • Author Affiliations

       

      SHWETA KUMARI1 SUNDARRAJ JAYAKUMAR1 SUBHASH C BIHANI1 NEENA SHETAKE1 2 RAJI NAIDU3 VIJAY K KUTALA4 HALADHAR D SARMA1 GAGAN D GUPTA1 2 SANTOSH K SANDUR1 2 VINAY KUMAR2

      1. Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
      2. Training School Complex, Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India
      3. Medical Division, Bhabha Atomic Research Centre, Mumbai 400 085, India
      4. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Hyderabad 500 082, India
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