title: Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro.
abstract: OBJECTIVE
  The emergence of multidrug-resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy.
  
  
  RESULTS
  Artonin I, a flavonoid obtained from Morus mesozygia Stapf., inhibited the bacterial efflux pump and induced depolarization of the cell membrane. To study the dose-dependent production of reactive oxygen species in MDR cells by artonin I, lucigenin chemiluminescence assay was employed. Reversal of multidrug resistance by artonin I, in combination with antibiotics, was measured by a fractional inhibitory concentration index assay. The effect of artonin I on ultrastructural features was studied by microscopy. Artonin I increased the penetration of ethidium bromide by blocking the efflux mechanism. It also helped anionic probe DiBAC4 (3) to bind with the lipid-rich cellular components by causing depolarization of the cell membrane. Artonin I reversed multidrug resistance and increased the susceptibility of existing antibiotics by lowering their minimum inhibitory concentrations (MICs).
  
  
  CONCLUSIONS
  Artonin I was identified both as a new antibacterial agent and a helper molecule to potentiate the action of otherwise inactive antibiotics.
  
  
  CONCLUSIONS
  Artonin I can be developed as potential antimicrobial and resistance reversal agent.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Farooq
authors.forename: A-T-
authors.initials: AT
authors.lastname: Wahab
authors.forename: C D A
authors.initials: CD
authors.lastname: Fozing
authors.forename: A-U-
authors.initials: AU
authors.lastname: Rahman
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004996:Ethidium / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000145:classification / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009504:Neutrophils / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D047309:Flavones; D017382:Reactive Oxygen Species; C000598610:artonin I; D004996:Ethidium
keywords: Morus mesozygiya Stapf.; artonin I; cell membrane depolarization; combination therapy; efflux pump inhibitor; flavonoid; multidrug-resistant Staphylococcus aureus; reactive oxygen species; reversal of multidrug resistance