Synthesis of cephalosporin-3′-diazeniumdiolates: biofilm dispersing NO-donor prodrugs activated by β-lactamase

Yepuri, Nageshwar R.; Barraud, Nicolas; Mohammadi, Nasim Shah; Kardak, Bharat G.; Kjelleberg, Staffan; Rice, Scott A.; Kelso, Michael J.

doi:10.1039/c3cc40869h

Cited by 55 publications

(65 citation statements)

References 17 publications

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“…SNP as an NO donor has been shown to deliver an effective NO concentration about 1,000-fold lower than the concentration of the donor over several minutes (up to 30 min) (22), whereas the half-life of MAHMA NONOate is much shorter (1 to 2 min) (39). More recently, prodrugs releasing NO after an activation step in the bacterium, such as diethylamine (DEA) NONOate-cephalosporin prodrug (DEACP), were also shown to promote dispersal (46,47).…”

Section: Properties and Sources Of Nomentioning

confidence: 99%

Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

Cutruzzolà

Frankenberg‐Dinkel

2016

J Bacteriol

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bThe formation of the organized bacterial community called biofilm is a crucial event in bacterial physiology. Given that biofilms are often refractory to antibiotics and disinfectants to which planktonic bacteria are susceptible, their formation is also an industrially and medically relevant issue. Pseudomonas aeruginosa, a well-known human pathogen causing acute and chronic infections, is considered a model organism to study biofilms. A large number of environmental cues control biofilm dynamics in bacterial cells. In particular, the dispersal of individual cells from the biofilm requires metabolic and morphological reprogramming in which the second messenger bis-(3=-5=)-cyclic dimeric GMP (c-di-GMP) plays a central role. The diatomic gas nitric oxide (NO), a well-known signaling molecule in both prokaryotes and eukaryotes, is able to induce the dispersal of P. aeruginosa and other bacterial biofilms by lowering c-di-GMP levels. In this review, we summarize the current knowledge on the molecular mechanisms connecting NO sensing to the activation of c-di-GMP-specific phosphodiesterases in P. aeruginosa, ultimately leading to c-di-GMP decrease and biofilm dispersal. PSEUDOMONAS AERUGINOSA: A MODEL SYSTEM FOR BIOFILM RESEARCH

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Section: Properties and Sources Of Nomentioning

confidence: 99%

Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

Cutruzzolà

Frankenberg‐Dinkel

2016

J Bacteriol

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“…In addition, novel carriers, including nanoparticles and dual-action hybrid drugs, polymer coatings and prodrugs specifically designed to release NO to biofilm infection sites are being investigated. In the future, new compounds will be designed that exhibit multiple actions, including Compound numbers correspond to [134]. Fig.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…In these experiments, the use of DEACP at 10 µM was found to be more effective than at 100 µM, increasing tobramycin and ciprofloxacin treatments by 1.8 and 1.5 log reduction in CFU, respectively [95]. The novel and 21 flexible synthetic chemistry route developed for DEACP was used to access five additional analogues carrying variations in both the acyl-amido side chain (R1) and O 2 -alkyldiazeniumdiolate (R2) portions [134] (Fig. 5).…”

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confidence: 99%

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Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Barraud¹,

Kelso²,

Rice

et al. 2014

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215

196

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Studies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. AbstractStudies of the biofilm life cycle can identify novel targets and strategies for improving biofilm control measures. Of particular interest are dispersal events, where a subpopulation of cells is released from the biofilm community to search out and colonize new surfaces. Recently, the simple gas and ubiquitous biological signaling molecule nitric oxide (NO) was identified as a key mediator of biofilm dispersal conserved across microbial species. Here, we review the role and mechanisms of NO mediating dispersal in bacterial biofilms, and its potential for novel therapeutics. In contrast to previous attempts using high dose NO aimed at killing pathogens, the use of low, non-toxic NO signals (picomolar to nanomolar range) to disperse biofilms represents an innovative and highly favourable approach to improve infectious disease treatments. Further, several NO-based technologies have been developed that offer a versatile range of solutions to control biofilms, including: (i) NO-generating compounds with short or long half-lives and safe or inert residues, (ii) novel compounds for the targeted delivery of NO to infectious biofilms during systemic treatments, and (iii) novel NO-releasing materials and surface coatings for the prevention and dispersal of biofilms. Overall the use of low levels of NO exploiting its signaling properties to induce dispersal represents an unprecedented and promising strategy for the control of biofilms in clinical and industrial contexts. 3 Increased antimicrobial tolerance in biofilms is the basis for chronic infecti...

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“…Exogenous genes that encode cell/tissue-specific enzymes, such as nitroreductase (Sharma et al, 2013), β-lactamase (Yepuri et al, 2013), glutathione-S-transferase (GST) (Weyerbrock et al, 2012), and β-galactosidase (Chen and Zhang, 2013), are employed to achieve NO release at target sites. A bacterial biofilm-targeted NO-releasing agent was designed with the capability of selectively releasing NO upon contact with enzyme β-lactamase (Yepuri et al, 2013). The locationspecific NO release could minimize the interruption of NO-associated side effects in normal tissue.…”

Section: Site-specific Delivery Of Controlled No-releasing Agentmentioning

confidence: 99%

Controlled nitric oxide release for tissue repair and regeneration

Nie¹,

2016

Turk J Biol

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The discovery that nitric oxide (NO) plays crucial roles in mammalian systems has spurred considerable interest in its translational application. However, the major problem with its application in clinical settings is the high reactivity of NO, which makes it difficult to supply NO with spatiotemporal accuracy while maintaining its bioactivity. To deliver NO at a specified rate to a preferred location for a precise period of time is highly demanded. The significant technological advancements in controlled release make it possible to control NO release at the target site with a sustained release rate and an optimum concentration, and then provide a longer therapeutic duration of NO. Moreover, biomaterials designed for regenerative applications provide carriers with support structures for controlled NO releasing. Meanwhile, engineered matrices with controlled NO release have been used as vehicles for stem cell delivery to enhance cell engraftment and further to improve therapeutic effects of transplanted cells. In this review, we will provide an overview of controlled NO release materials, as well as the mechanisms of their treatment effects in tissue-repairing processes. Furthermore, the application of on-demand NO-releasing materials as carriers for stem cell transplantation and the NO-based therapeutic applications in translational medicine will be discussed.

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Synthesis of cephalosporin-3′-diazeniumdiolates: biofilm dispersing NO-donor prodrugs activated by β-lactamase

Cited by 55 publications

References 17 publications

Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

Origin and Impact of Nitric Oxide in Pseudomonas aeruginosa Biofilms

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

Controlled nitric oxide release for tissue repair and regeneration

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