A role for reactive oxygen species in the antibacterial properties of carbon monoxide-releasing molecules

Tavares, Ana; Nobre, Lígia S.; Saraiva, Lı́gia M.

doi:10.1111/j.1574-6968.2012.02633.x

Cited by 39 publications

(28 citation statements)

References 79 publications

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“…The ruthenium-based CO-RMs appeared more effective and CORM-A1 only exerted a transient bacteriostatic action, highlighting again the importance of the metal in mediating some activities of CO-RMs and perhaps guiding CO to the appropriate cellular target. More detailed work has been performed to investigate the direct effect of CO-RMs on different bacteria and the results have been reviewed elsewhere [88,89]. …”

Section: Introductionmentioning

confidence: 99%

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

2012

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Carbon monoxide-releasing molecules (CO-RMs) are a class of organometallo compounds capable of delivering controlled quantities of CO gas to cells and tissues thus exerting a broad spectrum of pharmacological effects. CO-RMs containing transition metal carbonyls were initially implemented to mimic the function of heme oxygenase-1 (HMOX1), a stress inducible defensive protein that degrades heme to CO and biliverdin leading to anti-oxidant and anti-inflammatory actions. Ten years after their discovery, the research on the chemistry and biological activities of CO-RMs has greatly intensified indicating that their potential use as CO delivering agents for the treatment of several pathological conditions is feasible. Although CO-RMs are a class of compounds that structurally diverge from traditional organic-like pharmaceuticals, their behaviour in the biological environments is progressively being elucidated revealing interesting features of metal-carbonyl chemistry towards cellular targets. Specifically, the presence of carbonyl groups bound to transition metals such as ruthenium, iron or manganese appears to make CO-RMs unique in their ability to transfer CO intracellularly and amplify the mechanisms of signal transduction mediated by CO. In addition to their well-established vasodilatory activities and protective effects against organ ischemic damage, CO-RMs are emerging for their striking anti-inflammatory properties which may be the result of the multiple activities of metal carbonyls in the control of redox signaling, oxidative stress and cellular respiration. Here, we review evidence on the pharmacological effects of CO-RMs in models of acute and chronic inflammation elaborating on some emerging concepts that may help to explain the chemical reactivity and mechanism(s) of action of this distinctive class of compounds in biological systems.

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Section: Introductionmentioning

confidence: 99%

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

2012

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“…CORM-3 is bactericidal against a variety of microbes, including Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (10,12,13,30,40).…”

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confidence: 99%

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Mclean

Begg

Jesse

et al. 2013

Antioxidants & Redox Signaling

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Aims: Carbon monoxide (CO)-releasing molecules (CO-RMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically. One such application is antimicrobial activity; therefore, we aimed to characterize and compare the effects of the CO-RM, CORM-3, and its inactivated counterpart, where all labile CO has been removed, at the transcriptomic and cellular level. Results: We found that both compounds are able to penetrate the cell, but the inactive form is not inhibitory to bacterial growth under conditions where CORM-3 is. Transcriptomic analyses revealed that the bacterial response to inactivated CORM-3 (iCORM-3) is much lower than to the active compound and that a wide range of processes appear to be affected by CORM-3 and to a lesser extent iCORM-3, including energy metabolism, membrane transport, motility, and the metabolism of many sulfur-containing species, including cysteine and methionine. Innovation: This work has demonstrated that both CORM-3 and its inactivated counterpart react with cellular functions to yield a complex response at the transcriptomic level. A full understanding of the actions of both compounds is vital to understand the toxic effects of CO-RMs. Conclusion: This work has furthered our understanding of how CORM-3 behaves at the cellular level and identifies the responses that occur when the host is exposed to the Ru compound as well as those that result from the released CO. This is a vital step in laying the groundwork for future development of optimized CO-RMs for eventual use in antimicrobial therapy.

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“…Moreover, the transition metals in CORMs have been shown to trigger the formation of hydroxyl radicals from water oxygen in the presence of CO ligands (35,36). ROS have been shown to play a role in the bactericidal mechanism in E. coli (36) but not in P. aeruginosa (37).…”

Section: Discussionmentioning

confidence: 99%

“…Macromolecular systems have also been exploited as CORM carriers to adapt CO release kinetics and retain toxic metabolites after CO release (27 (10,(31)(32)(33)(34). Besides inhibition of the respiratory chain, CORMs seem to also target other proteins, because the bactericidal effects were found under aerobic and anaerobic conditions (33,35). CORMs are also known to induce oxidative stress (36), but the effect depends on the CORM and bacterial species (35).…”

Section: Discussionmentioning

confidence: 99%

Bactericidal Effect of a Photoresponsive Carbon Monoxide-Releasing Nonwoven against Staphylococcus aureus Biofilms

Klinger-Strobel

Gläser

Makarewicz

et al. 2016

Antimicrob Agents Chemother

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Staphylococcus aureus is a leading pathogen in skin and skin structure infections, including surgical and traumatic infections that are associated with biofilm formation. Because biofilm formation is accompanied by high phenotypic resistance of the embedded bacteria, they are almost impossible to eradicate by conventional antibiotics. Therefore, alternative therapeutic strategies are of high interest. We generated nanostructured hybrid nonwovens via the electrospinning of a photoresponsive carbon monoxide (CO)-releasing molecule [CORM-1, Mn 2 (CO) 10 ] and the polymer polylactide. This nonwoven showed a CO-induced antimicrobial activity that was sufficient to reduce the biofilm-embedded bacteria by 70% after photostimulation at 405 nm. The released CO increased the concentration of reactive oxygen species (ROS) in the biofilms, suggesting that in addition to inhibiting the electron transport chain, ROS might play a role in the antimicrobial activity of CORMs on S. aureus. The nonwoven showed increased cytotoxicity on eukaryotic cells after longer exposure, most probably due to the released lactic acid, that might be acceptable for local and short-time treatments. Therefore, CO-releasing nonwovens might be a promising local antimicrobial therapy against biofilm-associated skin wound infections. Staphylococcus aureus, both methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA), is the leading pathogen in skin and skin structure infections (SSSIs), including surgical and traumatic infections (1, 2). S. aureus has developed a highly effective mechanism to invade tissues and evade the immune system by biofilm formation and intracellular persistence. This can result in chronic and recurring SSSI, particularly in patients with comorbidities such as diabetes mellitus (e.g., diabetic foot syndrome). Noneradicable S. aureus SSSI can be the focus of S. aureus bacteremia, which has a mortality of up to 30% (3). In the United States, community-acquired MRSA has emerged as one of the leading causes of community-acquired SSSI (2).Biofilms are sessile matrix-embedded microbial communities that colonize nearly all artificial and natural surfaces. They are thought to be present in more than 80% of all nosocomial bacterial infections (4). Compared to their planktonic counterparts, bacteria embedded in a biofilm benefit from the protective properties of the matrix, conveying up to 1,000-fold-higher resistance to antibiotics (5). The enhanced phenotypic resistance (correctly termed tolerance) of biofilms is caused mainly by decreased growth rates and metabolically inactive persister cells (a protected phenotypic state) (6). Most antibiotics inhibit metabolic processes in the cell, such as replication (e.g., fluoroquinolones), transcription (e.g., rifampin) or translation (e.g., aminoglycosides and macrolides), and therefore they become ineffective in these persister cells. Altered microenvironments (7) and enzymes hydrolyzing or modifying the antimicrobials that are enriched within the matrix are additio...

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A role for reactive oxygen species in the antibacterial properties of carbon monoxide-releasing molecules

Cited by 39 publications

References 79 publications

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Bactericidal Effect of a Photoresponsive Carbon Monoxide-Releasing Nonwoven against Staphylococcus aureus Biofilms

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A role for reactive oxygen species in the antibacterial properties of carbon monoxide-releasing molecules

Cited by 39 publications

References 79 publications

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Analysis of the Bacterial Response to Ru(CO)3Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action

Bactericidal Effect of a Photoresponsive Carbon Monoxide-Releasing Nonwoven against Staphylococcus aureus Biofilms

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Analysis of the Bacterial Response to Ru(CO)₃Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action