Dataset Information

Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide.

ABSTRACT: Numerous materials have been developed to try and harness the antimicrobial properties of nitric oxide (NO). However, the short half-life and reactivity of NO have made precise, tunable delivery difficult. As such, conventional methodologies have generally relied on donors that spontaneously release NO at different rates, and delivery profiles have largely been constrained to decaying dynamics. In recent years, the possibility of finely controlling NO release, for instance with light, has become achievable and this raises the question of how delivery dynamics influence therapeutic potential. Here we investigated this relationship using Escherichia coli as a model organism and an approach that incorporated both experimentation and mathematical modeling. We found that the best performing delivery mode was dependent on the NO payload, and developed a mathematical model to quantitatively dissect those observations. Those analyses suggested that the duration of respiratory inhibition was a major determinant of NO-induced growth inhibition. Inspired by this, we constructed a delivery schedule that leveraged that insight to extend the antimicrobial activity of NO far beyond what was achievable by traditional delivery dynamics. Collectively, these data and analyses suggest that the delivery dynamics of NO have a considerable impact on its ability to achieve and maintain bacteriostasis.

SUBMITTER: Sivaloganathan DM

PROVIDER: S-EPMC7181900 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide.

Sivaloganathan Darshan M DM Brynildsen Mark P MP

Frontiers in physiology 20200417

Numerous materials have been developed to try and harness the antimicrobial properties of nitric oxide (NO). However, the short half-life and reactivity of NO have made precise, tunable delivery difficult. As such, conventional methodologies have generally relied on donors that spontaneously release NO at different rates, and delivery profiles have largely been constrained to decaying dynamics. In recent years, the possibility of finely controlling NO release, for instance with light, has become ...[more]

PMID: 32362838

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Project description:In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might provide an interesting way to characterize the extent of BC in unhealthy patients.

Dataset Information

Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide.

Publications

Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide.

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