Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)₃(tpa-κ³N)]⁺Against a PathogenicEscherichia colithat Causes Urinary Infections

Abstract

Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa-κ3N)]+) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. Results: 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. Innovation: 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. Conclusion: 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.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…For example, Nobre et al reported that the administration of CO gas into the growing cultures could cause significant impairment to the growth of Escherichia coli and Staphylococcus aureus . Recently, CORMs with the capacity of delivering CO directly to intracellular targets have been used as bactericides against a wide range of microorganisms, such as Pseudomonas aeruginosa , Mycobacterium tuberculosis , Helicobacter pylori , pathogenic Escherichia coli , and Neisseria gonorrhoeae . Importantly, CORMs were shown to be more potent bactericides than CO gas due to the accumulation of CORMs inside bacterial cells .…”

Light- or oxidation-triggered CO release from [MnI(CO)3(κ3-L)] complexes: reaction intermediates and a new synthetic route to [MnIII/IV2(μ-O)2(L)2] compounds

“…as model systems for known manganese based metalloenzymes like Mn-catalase, arginase 8,9 or the OEC in PSII. 7,10 To probe this concept, we additionally investigated the light-triggered CO substitution for the Mn I -carbonyl complex 3, which is also already well investigated as photoCORM 11 and for its therapeutic use, 12 bearing the potentially tetradentate trispyridylmethylamin (tpa) ligand, for which µ-oxido bridged Mn III /Mn IV complexes of high catalase activity have already been reported. 13…”

Visible Light-Activated PhotoCORMs

“…Taken together, the results showed promising steps for the use of photoCORMs as drug templates for the treatment of breast cancer. Tinajero and coworkers reported an Mn-based photoactivated CORM which reduces growth and viability of Escherichia coli, only by light induction [56]. They demonstrated that CO binds to specific intracellular sites, namely, respiratory oxidases and a globin protein expressed in a particular strain, while the Mn metal center is not accumulated in the cells.…”