Potential application of gaseous nitric oxide as a topical antimicrobial agent

Ghaffari, Abdi; Miller, Christopher C.J.; McMullin, Bevin; Ghahary, Aziz

doi:10.1016/j.niox.2005.08.003

Cited by 203 publications

(192 citation statements)

References 50 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…At elevated concentrations, the high diffusivity and multiple modes of action of NO make it a broad-spectrum antimicrobial agent that could kill biofilms of Gramnegative and Gram-positive bacteria. In vitro experiments showed that exposure to 200 ppm NO gas (~8 µM NO) for up to 5 h could fully eradicate cultures of clinical isolates of S. aureus, methicillin-resistant S. aureus (MRSA), E. coli, Group B Streptococcus, P. aeruginosa and Candida albicans [97]. The potential of intermittent exposure to high levels of NO gas has been assessed in animal trials using rats.…”

mentioning

confidence: 99%

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

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

221

196

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 99%

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

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

221

196

View full text Add to dashboard Cite

show abstract

“…13 Both grampositive and gram-negative bacteria have been found to be susceptible to gaseous NO, including methicillin-resistant Staphylococcus aureus (MRSA). 14 The doses of NO required to kill bacteria proved non-toxic to human dermal fibroblasts. Using diazeniumdiolate small molecule NO donors, Raulli et al reported the minimum inhibitory concentrations against several bacterial species.…”

mentioning

confidence: 99%

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Hetrick

Shin²,

Stasko³

et al. 2008

ACS Nano

322

380

View full text Add to dashboard Cite

The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.Keywords nitric oxide; silica nanoparticle; antibacterial; bactericidal; cytotoxicity; reactive nitrogen species; reactive oxygen species Antibiotic resistance has resulted in bacterial infections becoming the most common cause of infectious disease-related death. 1,2 In the United States alone, nearly 2 million people per year acquire infections during a hospital stay, of which approximately 90,000 die. 2 The primary culprits behind such deadly infections are antibiotic-resistant pathogens, which are responsible for approximately 70% of all lethal nosocomial infections. The growing danger of life-threatening infections and the rising economic burden of resistant bacteria have created a demand for new antibacterial therapeutics.The use of nanoparticles as delivery vehicles for bactericidal agents represents a new paradigm in the design of antibacterial therapeutics. To date, most antibacterial nanoparticles have been engineered using traditional antibiotics that are either incorporated within the particle scaffold or attached to the exterior of the particle. In many cases, such particles have exhibited greater efficacy than their constituent antibiotics alone. For example, Gu et al. reported that vancomycin-capped gold nanoparticles exhibited a 64-fold improvement in efficacy over vancomycin alone. 3 Similarly, silver nanoparticles have schoenfisch@unc.edu. Supporting Information Available: Synthesis of FITC-modified silica nanoparticles, AFM analysis of nanoparticle dimensions, scavenging of NO by TSB, and confocal fluorescence microscopy images of PROLI/NO-treated P. aeruginosa cells. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2013 February 13. shown greater antibacterial activity than silver ion (Ag + ) in solution due to the direct toxicity of the particles and tunable release of Ag + based on nanocomposite size. [4][...

show abstract

“…However, site-specific delivery of this reactive gas in high doses to combat chronic infection and neoplasms still remains a challenge. Although delivery of gaseous NO directly to infected wounds has shown promise [58,59], handling of this noxious and highly diffusible gas in a hospital setting presents a discouraging task in general. In our research, both control on the dosage of NO through light-triggering and delivery to specific sites through entrapment of the photoactive nitrosyls in material hosts of various forms (patch, bandage and powder) have been achieved.…”

Section: Resultsmentioning

confidence: 99%

Light-triggered nitric oxide delivery to malignant sites and infection

Heilman

Mascharak

2013

Phil. Trans. R. Soc. A.

View full text Add to dashboard Cite

The discovery of nitric oxide (NO) as a signalling molecule in various physiological and pathological pathways has spurred research in the design of exogenous NO donors as drugs. In recent years, metal nitrosyls (NO complexes of metals) have been investigated as NO-donating agents. Results from our laboratory during the past few years have demonstrated that metal nitrosyls derived from designed ligands can deliver NO under the total control of light of various frequencies. Careful incorporation of these photoactive nitrosyls into polymer matrices has afforded a set of nitrosylpolymer composites that can be used to make such NO delivery site-specific. The composite materials have shown excellent antineoplastic and antimicrobial actions in several in vitro experiments. This review highlights our key results in the context of recent developments in this area of NO donors that deliver NO on demand.

show abstract

Potential application of gaseous nitric oxide as a topical antimicrobial agent

Cited by 203 publications

References 50 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

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Light-triggered nitric oxide delivery to malignant sites and infection

Contact Info

Product

Resources

About