Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plate

Finnen, Michael J.; Hennessy, Alison; McLean, Susannah; Bisset, Yvonne; Mitchell, Rory; Megson, Ian L.; Weller, Richard

doi:10.1111/j.1365-2133.2007.08063.x

Cited by 15 publications

(11 citation statements)

References 32 publications

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“…These include as an anti-fungal agent in nails [139] and as a therapeutic agent in cystic fibrosis [128]. Topical administration of GSNO was shown to improve onychomycosis through an S-nitrosothiol-dependent mechanism [139]. This is particularly noteworthy, as the nail bed represents a physical barrier impenetrable to many anti-fungal agents.…”

Section: Use Of Gsno In Human Clinical Trialsmentioning

confidence: 99%

S-Nitrosoglutathione

Broniowska

Diers

Hogg

2013

Biochimica et Biophysica Acta (BBA) - General Subjects

309

290

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Background S-Nitrosoglutathione (GSNO) is the S-nitrosated derivative of glutathione and is thought to be a critical mediator of the down-stream signaling effects of nitric oxide (NO). GSNO has also been implicated as a contributor to various disease states. Scope of Review This review focuses on the chemical nature of GSNO, its biological activities, the evidence that it is an endogenous mediator of NO action, and implications for therapeutic use. Major Conclusions GSNO clearly exerts its cellular actions through both NO- and S-nitrosation-dependent mechanisms; however, the chemical and biological aspects of this compound should be placed in the context of S-nitrosation as a whole. General Significance GSNO is a central intermediate in formation and degradation of cellular S-nitrosothiols with potential therapeutic applications; thus, it remains an important molecule of study.

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Section: Use Of Gsno In Human Clinical Trialsmentioning

confidence: 99%

S-Nitrosoglutathione

Broniowska

Diers

Hogg

2013

Biochimica et Biophysica Acta (BBA) - General Subjects

309

290

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“…Especially toxic are the products of the interactions between ROS and RNS, such as peroxynitrite, generated in macrophages by the reaction of nitric oxide with superoxide (McLean et al 2010;Prolo et al 2014). Moreover, NO reacts with cysteine thiols to form S-nitrosothiols (SNO), an effective inhibitor of Gram-positive bacteria and fungi (Finnen et al 2007;Cariello et al 2012). C. albicans is therefore exposed to a variety of toxic ROS, RNS, and RSS-related molecules and byproducts that it responds to in mechanistically distinct ways.…”

mentioning

confidence: 99%

Adaptation of Candida albicans to Reactive Sulfur Species

Chebaro

Lorenz²,

et al. 2017

Genetics

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Candida albicans is an opportunistic fungal pathogen that is highly resistant to different oxidative stresses. How reactive sulfur species (RSS) such as sulfite regulate gene expression and the role of the transcription factor Zcf2 and the sulfite exporter Ssu1 in such responses are not known. Here, we show that C. albicans specifically adapts to sulfite stress and that Zcf2 is required for that response as well as induction of genes predicted to remove sulfite from cells and to increase the intracellular amount of a subset of nitrogen metabolites. Analysis of mutants in the sulfate assimilation pathway show that sulfite conversion to sulfide accounts for part of sulfite toxicity and that Zcf2-dependent expression of the SSU1 sulfite exporter is induced by both sulfite and sulfide. Mutations in the SSU1 promoter that selectively inhibit induction by the reactive nitrogen species (RNS) nitrite, a previously reported activator of SSU1, support a model for C. albicans in which Cta4-dependent RNS induction and Zcf2-dependent RSS induction are mediated by parallel pathways, different from S. cerevisiae in which the transcription factor Fzf1 mediates responses to both RNS and RSS. Lastly, we found that endogenous sulfite production leads to an increase in resistance to exogenously added sulfite. These results demonstrate that C. albicans has a unique response to sulfite that differs from the general oxidative stress response, and that adaptation to internal and external sulfite is largely mediated by one transcription factor and one effector gene.

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“…It has been previously suggested that the antifungal actions of acidified nitrites are mediated by S ‐nitrosothiols formed by reaction of thiol groups in the toe‐nail with the acidified nitrites (Finnen et al . ). Another suggested explanation was that the combination of NO and reactive oxygen species produces intermediates, such as peroxynitrite, which are far more potent microbiocidal agents than their precursors (Fang ).…”

Section: Discussionmentioning

confidence: 97%

“…NO gas was shown to have antimicrobial activity against wide variety of bacteria (McMullin et al 2005;Ghaffari et al 2006) and fungi (Wang and Higgins 2005;Finnen et al 2007;Lazar et al 2008). It has also been reported that a short-term exposure to 50-500 ppm of NO was able to inhibit mycelial growth, sporolation and germination of postharvest horticulture fungi (Lazar et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…It is predicted that nitric oxide will attach to surface cysteines causing the formation of S-nitrosylation (-SNO) sites which perturb enzyme structure and/or catalytic activity (Darling and Evans 2003). It has been previously suggested that the antifungal actions of acidified nitrites are mediated by S-nitrosothiols formed by reaction of thiol groups in the toe-nail with the acidified nitrites (Finnen et al 2007). Another suggested explanation was that the combination of NO and reactive oxygen species produces intermedi-ates, such as peroxynitrite, which are far more potent microbiocidal agents than their precursors (Fang 1997).…”

Section: Discussionmentioning

confidence: 99%

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A nitric oxide-releasing solution as a potential treatment for fungi associated with tinea pedis

2012

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Aims: To test a nitric oxide-releasing solution (NORS) as a potential antifungal footbath therapy against Trichophyton mentagrophytes and Trichophyton rubrum during the mycelial and conidial phases. Methods and Results: NORS (sodium nitrite citric acid) produces nitric oxide verified by gas chromatography and mass spectrometry (GC-MS). Antifungal activity of this solution was tested against mycelia and conidia of T. mentagrophytes and T. rubrum, using 1-20 mmol l À1 nitrites and 10-30 min exposure times. The direct effect of the gas released from the solution on the viability of those fungi was tested. NORS demonstrated strong antifungal activity and was found to be dose and time dependent. NO and nitrogen dioxide (NO 2 ) were the only gases detected from this reaction and are likely responsible for the antifungal effect. Conclusions: This in vitro research suggests that a single 20-min exposure to NORS could potentially be used as an effective single-dose treatment against fungi that are associated with tinea pedis in both mycelia and spore phase. Significance and Impact of the Study: This study provides the background for developing a user-friendly footbath treatment for Athlete's Foot that will kill both vegetative fungi and its spores.

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Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plate

Cited by 15 publications

References 32 publications

S-Nitrosoglutathione

S-Nitrosoglutathione

Adaptation of Candida albicans to Reactive Sulfur Species

A nitric oxide-releasing solution as a potential treatment for fungi associated with tinea pedis

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