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Nitrogen dioxide: from a simple diffusible gas to a potential antibacterial against P. fluorescens?

Abstract : Nitrogen dioxyde (NO2) and nitrogen oxide (NO), mostly produced by anthropogenic activities, are two major air pollutants [1]. An exposure to both compounds can lead to several deleterious impacts on human health (lung, cardio-and respiratory systems, brain) [2]. NO and NO2 exhibit a high reactivity with a wide range of cellular components (DNA, proteins, lipids, respiratory chain enzymes) which then alter the physiology of cells (eukaryotic or prokaryotic) when a bearable threshold is exceeded [3-6]. However, NO is also endogenously produced by a wide range of organisms (mammals, bacteria, plants) and interplays a fundamental mediator role in various physiological pathways [7-8]. Indeed, in mammals NO mediates muscle relaxation, neurotransmission and also innate immunity [9-11]. This last process can be modulated by NO itself or more reactive derived compounds such as NO2. Thus, an emergence of therapeutics were developed targeting NO-pathway such as NO-donnors and NO synthesis inhibitors compounds [12]. During the past decades, the excessive use of antibiotics led to an emergence of threatening multi-resistant bacteria in the medical field. More recently, a new promising therapy using inhaled gaseous NO (gNO) in the case of infections in pneumopathologies was investigated [13]. Thence, NO is placed as a potent antibacterial agent. However, few data are yet available concerning on the potential use of gaseous NO2 as antibacterial agent. Here we wanted to highlight the direct effect of this gas on an environmental strain P. fluorescens, MFAF76a, exhibiting virulent traits toward pulmonary cells [14]. Two concentrations of NO2 were investigated respectively 0.2 and 45ppm. Cultivability tests and growth kinetics demonstrate the cytotoxicity of NO2 at 45ppm. Then, the integrity of the bacterial membrane was measured trough an exhaustive lipidomic study (HPTLC coupled with MALDI-TOF MS/MSI, Live dead tests, FAME) [14-15]. At 45ppm an alteration of the membrane was observed, potentially correlated to the loss of an unknown glycerophospholipid. Moreover an increase in permeability was noticed. Then, a transcriptomic study revealed a modified expression at 45ppm of genes implicated : (i) in parietal stress response (ii) in detoxification, (iii) in social behavior and (iv) in antibiotic resistance [16]. Thus, physiological were performed to confirm these data. Biofilms observed by CLSM highlighted a modification in their formation. However, the strain became more virulent since an increase in motility and in resistance to aminoglycoside antibiotics was observed [16]. This study highlights here the high complexity of NO and NO2 due to their high reactivity and two-side effects. The next step of this project will be now to find a more appropriate concentration for a NO2-treatment leading to increase the cytotoxic effect of this gas and reducing the emergence of virulent traits in this highly adaptive strain.
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Contributor : Cécile Duclairoir Poc <>
Submitted on : Friday, November 15, 2019 - 4:14:30 PM
Last modification on : Saturday, November 16, 2019 - 1:36:33 AM

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  • HAL Id : hal-02360955, version 1

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Segolene Depayras, Tatiana Kondakova, Hermann J. Heipieper, Marc Feuilloley, Nicole Orange, et al.. Nitrogen dioxide: from a simple diffusible gas to a potential antibacterial against P. fluorescens?. 21ème Journée de l’EdNBISE, Mar 2018, Rouen, France. ⟨hal-02360955⟩

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