title: Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)3(tpa-κ(3)N)](+) Against a Pathogenic Escherichia coli that Causes Urinary Infections.
abstract: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa-κ(3)N)](+)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli.
  
  
  
  Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline.
  
  
  
  The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated.
  
  
  
  The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents. Antioxid. Redox Signal. 24, 765-780.
authors: 1 Department of Molecular Biology and Biotechnology, The University of Sheffield , Sheffield, United Kingdom .
authors: Mariana
authors: M
authors: Tinajero-Trejo
authors: 1 Department of Molecular Biology and Biotechnology, The University of Sheffield , Sheffield, United Kingdom .
authors: Namrata
authors: N
authors: Rana
authors: 2 Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg , Würzburg, Germany .
authors: Christoph
authors: C
authors: Nagel
authors: 1 Department of Molecular Biology and Biotechnology, The University of Sheffield , Sheffield, United Kingdom .
authors: Helen E
authors: HE
authors: Jesse
authors: 3 Department of Chemistry, The University of Sheffield , Sheffield, United Kingdom .
authors: Thomas W
authors: TW
authors: Smith
authors: 1 Department of Molecular Biology and Biotechnology, The University of Sheffield , Sheffield, United Kingdom .
authors: Lauren K
authors: LK
authors: Wareham
authors: 3 Department of Chemistry, The University of Sheffield , Sheffield, United Kingdom .
authors: Michael
authors: M
authors: Hippler
authors: 2 Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg , Würzburg, Germany .
authors: Ulrich
authors: U
authors: Schatzschneider
authors: 1 Department of Molecular Biology and Biotechnology, The University of Sheffield , Sheffield, United Kingdom .
authors: Robert K
authors: RK
authors: Poole
mesh_terms: D000332:Aerobiosis; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D010101:Oxygen Consumption; D055668:Photochemical Processes; D013890:Thiourea / Q000494:pharmacology; D014466:Ultraviolet Rays; D014552:Urinary Tract Infections / Q000382:microbiology*
chemical_list: C000621370:(Mn(CO)3(tpa-kappa3N))Br; D000900:Anti-Bacterial Agents; D056831:Coordination Complexes; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide; D013890:Thiourea