Synergistic Effects between Conventional Antibiotics and 2-Aminoimidazole-Derived Antibiofilm Agents

Rogers, Steven A.; Huigens, Robert W.; Cavanagh, John; Melander, Christian

doi:10.1128/aac.01418-09

Cited by 183 publications

(154 citation statements)

References 38 publications

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“…For instance, 2-aminoimidazole derivatives targeting QS have been designed and found to disperse established biofilms [40,41]. Proof of concept studies showed that in vivo manipulation of c-di-GMP levels can effectively clear (by decreasing c-di-GMP) or prolong (by increasing c-di-GMP) Pseudomonas aeruginosa infections in murine models [42,43].…”

Section: Inducing the Natural Biofilm Dispersal Response To Control Bmentioning

confidence: 99%

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

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

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: Inducing the Natural Biofilm Dispersal Response To Control Bmentioning

confidence: 99%

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

Barraud¹,

Kelso²,

Rice

et al. 2014

CPD

215

196

View full text Add to dashboard Cite

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“…This leads to a perpetual state of inflammation that delays wound healing (4,5). It is estimated that more than 90% of all chronic wounds contain bacteria that are biofilm associated (6), making them up to 1,000-fold more tolerant to antibiotics and the host immune response (7). Thus, taking into account the alarming increase of antibiotic-resistant bacteria, the added ability of pathogens to reside within the protection of the biofilm matrix all too often makes effective treatment of these infections impossible.…”

mentioning

confidence: 99%

Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds

Fleming

Chahin

Rumbaugh

2017

Antimicrob Agents Chemother

152

153

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The persistent nature of chronic wounds leaves them highly susceptible to invasion by a variety of pathogens that have the ability to construct an extracellular polymeric substance (EPS). This EPS makes the bacterial population, or biofilm, up to 1,000-fold more antibiotic tolerant than planktonic cells and makes wound healing extremely difficult. Thus, compounds which have the ability to degrade biofilms, but not host tissue components, are highly sought after for clinical applications. In this study, we examined the efficacy of two glycoside hydrolases, ␣-amylase and cellulase, which break down complex polysaccharides, to effectively disrupt Staphylococcus aureus and Pseudomonas aeruginosa monoculture and coculture biofilms. We hypothesized that glycoside hydrolase therapy would significantly reduce EPS biomass and convert bacteria to their planktonic state, leaving them more susceptible to conventional antimicrobials. Treatment of S. aureus and P. aeruginosa biofilms, grown in vitro and in vivo, with solutions of ␣-amylase and cellulase resulted in significant reductions in biomass, dissolution of the biofilm, and an increase in the effectiveness of subsequent antibiotic treatments. These data suggest that glycoside hydrolase therapy represents a potential safe, effective, and new avenue of treatment for biofilm-related infections.

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“…Their resistance against most therapeutic approaches comes from multiple mechanisms, including an exopolysaccharide matrix, which functions as a barrier against penetration of antimicrobial agents (20). Therefore, for an antimicrobial agent to be effective against bacteria such as A. baumannii, it is important for the compound to possess properties which lead to the dispersion and/or disruption of biofilm structures, leading to access to bacteria, such as that seen when bacteria are in the drugsensitive planktonic form (33). To this end, we evaluated the effects of N5 on the metabolic activity of A. baumannii in biofilms via scanning electron microscopy and observed extensive dispersion and disruption of the biofilm structure compared to untreated controls.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Activity of Nanoemulsion in Combination with Cetylpyridinium Chloride in Multidrug-Resistant Acinetobacter baumannii

Hwang¹,

Ramalingam

Bienek³

et al. 2013

Antimicrob Agents Chemother

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c Acinetobacter baumannii has emerged as a serious problematic pathogen due to the ever-increasing presence of antibiotic resistance, demonstrating a need for novel, broad-spectrum antimicrobial therapeutic options. Antimicrobial nanoemulsions are emulsified mixtures of detergent, oil, and water (droplet size, 100 to 800 nm) which have broad antimicrobial activity against bacteria, enveloped viruses, and fungi. Here, we screened the antimicrobial activities of five nanoemulsion preparations against four Acinetobacter baumannii isolates to identify the most suitable preparation for further evaluation. Among them, N5, which contains 10% (vol/vol) Triton X-100, 25% (vol/vol) soybean oil, and 1% (wt/vol) cetylpyridinium chloride (CPC), showed the best efficacy against A. baumannii in both its planktonic and biofilm forms and was selected for further study. Our data demonstrate that, while the killing of planktonic forms of A. baumannii was due to the 1% CPC component of our nanoemulsions, the breakdown of biofilms was achieved via the emulsified oil and detergent fractions. Furthermore, we documented the effect of ethanol and NaCl in combination with N5 on planktonic A. baumannii. In killing curves of N5 combined with other agents (ethanol or NaCl), a synergistic effect of a >2-log decrease in CFU/ml was observed. The antibiofilm activity of N5 was confirmed via a cell proliferation test and scanning electron microscopy. The effects of exposure to severe environmental conditions, which simulates the field conditions in Iraq and Afghanistan, were evaluated, and this exposure did not affect the overall antimicrobial activity of N5. These studies lay a solid foundation for the utilization of nanoemulsions against the antibiotic-resistant forms of A. baumannii.

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Synergistic Effects between Conventional Antibiotics and 2-Aminoimidazole-Derived Antibiofilm Agents

Cited by 183 publications

References 38 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

Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds

Antimicrobial Activity of Nanoemulsion in Combination with Cetylpyridinium Chloride in Multidrug-Resistant Acinetobacter baumannii

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