NO News Is Good News

Culotta, Elizabeth; Koshland, Daniel E.

doi:10.1126/science.1361684

Cited by 761 publications

(483 citation statements)

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“…First discovered in the 1980s for its role in regulating vasodilation via the activation of soluble guanylate cyclase, NO has since emerged as a universal signal regulating a plethora of physiological functions in living organisms [157]. Its importance in human physiology was recognised with a number of awards and NO was named 'molecule of the year' by Science in 1992 [158]. The diffusivity of NO across cell membranes and its reactivity towards a range of target sites stand out as unique properties in signal transduction that allow rapid spreading and amplification of an initial cue and the coordination of a subset of adjacent cells.…”

Section: Future Perspectivesmentioning

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: Future Perspectivesmentioning

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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“…This chemistry has been studied extensively because of the dietary and environmental exposure of humans to these substances [3][4][5]. Toxicological studies of deamination became more significant when it was recognized that endogenous nitric oxide [6,7] causes nitrosation [8,9], and that this process is accelerated by chronic inflammatory diseases [10,11]. It has been known for a long time that deamination of adenine 1, guanine 2, and cytosine 3 (Scheme 1) results in the formation of hypoxanthine, xanthine, and uracil, respectively, and these products are thought to result from DNA base diazonium ions 4-6, respectively, by direct nucleophilic dediazoniation.…”

mentioning

confidence: 99%

Ammonia elimination from protonated nucleobases and related synthetic substrates

Qian

Yang

et al. 2007

J. Am. Soc. Mass Spectrom.

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The results are reported of mass-spectrometric studies of the nucleobases adenine 1h (1, R ϭ H), guanine 2h, and cytosine 3h. The protonated nucleobases are generated by electrospray ionization of adenosine 1r (1, R ϭ ribose), guanosine 2r, and deoxycytidine 3d (3, R ϭ deoxyribose) and their fragmentations were studied with tandem mass spectrometry. In contrast to previous EI-MS studies of the nucleobases, NH 3 elimination does present a major path for the fragmentations of the ions [1h ϩ H] ϩ , [2h ϩ H] ϩ , and [3h ϩ H] ϩ . The ion [2h ϩ H Ϫ NH 3 ] ϩ also was generated from the acyclic precursor 5-cyanoamino-4-oxomethylenedihydroimidazole 13h and from the thioether derivative 14h of 2h (NH 2 replaced by MeS). The analyses of the modes of initial fragmentation is supported by density functional theoretical studies. Conjugate acids 15-55 were studied to determine site preferences for the protonations of 1h, 2h, 3h, 13h, and 14h. The proton affinity of the amino group hardly ever is the substrate's best protonation site, and possible mechanisms for NH 3 elimination are discussed in which the amino group serves as the dissociative protonation site. The results provide semi-direct experimental evidence for the existence of the pyrimidine ring-opened cations that we had proposed on the basis of theoretical studies as intermediates in nitrosative nucleobase deamination. [1,2]. This chemistry has been studied extensively because of the dietary and environmental exposure of humans to these substances [3][4][5]. Toxicological studies of deamination became more significant when it was recognized that endogenous nitric oxide [6,7] causes nitrosation [8,9], and that this process is accelerated by chronic inflammatory diseases [10,11]. It has been known for a long time that deamination of adenine 1, guanine 2, and cytosine 3 (Scheme 1) results in the formation of hypoxanthine, xanthine, and uracil, respectively, and these products are thought to result from DNA base diazonium ions 4-6, respectively, by direct nucleophilic dediazoniation. The discovery of oxanine formation [12][13][14] in the nitrosative deamination of guanine challenged the generality and completeness of this mechanism. Theoretical studies revealed that unimolecular dediazoniation of guaninediazonium ion 5 is accompanied or immediately followed by pyrimidine ringopening [15,16] and that cytosine-catalysis promotes the process [17,18]. The resulting 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazole is a highly reactive intermediate and undergoes acid-catalyzed 1,4-addition via cyano-N or imino-N protonated 5-cyanoimino-4-oxomethylene-4,5-dihydroimidazoles, 9 and 10, respectively [19].Labeling studies support this reaction mechanism for oxanine formation [20]. Moreover, we synthesized 5-cyanoamino-4-imidazolecarboxamide and studied its cyclization chemistry [21] and its proficiency for cross-link formation [22]. The unimolecular dediazoniation of the diazonium ions of adenine and cytosine can proceed without ring-opening but the cations 7 and 11 formed in this...

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“…One of the most active research areas in biological science, at present, is elucidation of the crucial and beneficial effects of nitric oxide in the human body (Culotta & Koshland, 1992;Feldman et al, 1993). Nitric oxide has been discovered to be a biological messenger important in the physiological functions of neurotransmission, blood clotting, blood pressure control, and in the immune system's ability to kill tumor cells and intracellular parasites.…”

Section: Nitric Oxidementioning

confidence: 99%

Composition and safety of cured meats in the USA

Cassens

1997

Food Chemistry

106

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NO News Is Good News

Abstract: A startlingly simple molecule unites neuroscience, physiology, and immunology, and revises scientists' understanding of how cells communicate and defend themselves.

Cited by 761 publications

References 1 publication

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

Ammonia elimination from protonated nucleobases and related synthetic substrates

Composition and safety of cured meats in the USA

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