Cephalosporin‐3′‐diazeniumdiolates: Targeted NO‐Donor Prodrugs for Dispersing Bacterial Biofilms

Barraud, Nicolas; Kardak, Bharat G.; Yepuri, Nageshwar R.; Howlin, Robert P.; Webb, Jeremy S.; Faust, Saul N; Kjelleberg, Staffan; Rice, Scott A.; Kelso, Michael J.

doi:10.1002/anie.201202414

Cited by 141 publications

(96 citation statements)

References 26 publications

(29 reference statements)

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“…While exposure to low doses of NO alone appears to be non-toxic to bacteria, the released planktonic cells and cells still residing on surfaces both show increased susceptibility to a range of antibiotics and antimicrobials [23, 39,95]. Thus NO-based anti-biofilm strategies probably benefit from combined treatments with standard antibiotic therapies to clear infections.…”

Section: Treatments To Induce Biofilm Dispersal With No and Effectivementioning

confidence: 99%

“…Interestingly, release of NO was also triggered by non-β-lactamase-producing E. coli extracts suggesting that the compounds can also be activated by transpeptidases, the target enzymes of β-lactam antibiotics. These compounds were effective at dispersing biofilms of several pathogenic species including mixed species biofilms from CF sputum, and when used in combination with tobramycin and ciprofloxacin greatly improved the outcome of the antibiotic therapy [53,95]. 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].…”

Section: Targeted Delivery Of No By Using β-Lactam Prodrug Antibioticsmentioning

confidence: 99%

“…These compounds were effective at dispersing biofilms of several pathogenic species including mixed species biofilms from CF sputum, and when used in combination with tobramycin and ciprofloxacin greatly improved the outcome of the antibiotic therapy [53,95]. 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.…”

Section: Targeted Delivery Of No By Using β-Lactam Prodrug Antibioticsmentioning

confidence: 99%

“…The compounds could potentially have side effects and these typically polar chemicals would be difficult to deliver to biofilms. An innovative new class of NO-donor prodrugs was recently described that can liberate NO upon specific activation by bacterial enzymes [95,134] (Fig. 4).…”

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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

CPD

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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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Section: Treatments To Induce Biofilm Dispersal With No and Effectivementioning

confidence: 99%

Section: Targeted Delivery Of No By Using β-Lactam Prodrug Antibioticsmentioning

confidence: 99%

Section: Targeted Delivery Of No By Using β-Lactam Prodrug Antibioticsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

Self Cite

215

196

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“…The use of NO donor compounds, such as diazeniumdiolates, have been a popular method of introducing NO into a biological system and have been be successfully employed to disperse P. aeruginosa biofilms. 100,251,[278][279][280] NO-donor compounds offer a controlled method of NO application and are able to stabilize the developing radical until its release. [281][282][283][284][285] Another class of molecule that has been found to inhibit biofilm formation and induce dispersal are nitroxides.…”

mentioning

confidence: 99%

Heteroorganic molecules and bacterial biofilms: Controlling biodeterioration of cultural heritage

Alexander¹,

Schiesser²

2016

Arkivoc

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Photoactive Lanthanide‐Based Upconverting Nanoclusters for Antimicrobial Applications

Kandoth

Barman

Chatterjee

et al. 2021

Adv Funct Materials

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Developing photoactive nanosystems against microbial infection and its therapeutic application is compromised by the lack of suitable materials or molecular dyes activatable at biofriendly NIR light. In this direction, the upconverting nanoparticles based on core–shell lanthanide‐doped nanoclusters are developed synthetically to achieve a broad range of NIR‐active phototherapeutic antimicrobial agents. This review illustrates antimicrobial photodynamic therapy (aPDT) and multimodal therapy by NIR photoirradiation, generated by lanthanum doped upconverting nanoparticles (UCNPs). The objective herein is to discuss the insights in developing the UCNPs for designing efficient aPDTs and their efficacies against emerging antibiotic‐resistant bacterial colonies and their biofilms, drug‐resistant fungi, and viruses. The biosafety and biocompatibility of UCNPs at both in vitro and in vivo level are also presented in detail. Finally, our perspectives on the ways of future material engineering needed for the effective translation into their real‐world applications are also commented.

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Cephalosporin‐3′‐diazeniumdiolates: Targeted NO‐Donor Prodrugs for Dispersing Bacterial Biofilms

Cited by 141 publications

References 26 publications

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

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

Heteroorganic molecules and bacterial biofilms: Controlling biodeterioration of cultural heritage

Photoactive Lanthanide‐Based Upconverting Nanoclusters for Antimicrobial Applications

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