Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide
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...
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doaj-9f28b02022494a4b970bb317438bcc942020-11-25T03:00:55ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-04-011110.3389/fphys.2020.00330520317Quantitative Modeling Extends the Antibacterial Activity of Nitric OxideDarshan M. Sivaloganathan0Mark P. Brynildsen1Program in Quantitative and Computational Biology, Princeton University, Princeton, NJ, United StatesDepartment of Chemical and Biological Engineering, Princeton University, Princeton, NJ, United StatesNumerous 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.https://www.frontiersin.org/article/10.3389/fphys.2020.00330/fullEscherichia coliHmpflavohemoglobinNOrespirationbacteriostatic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Darshan M. Sivaloganathan Mark P. Brynildsen |
spellingShingle |
Darshan M. Sivaloganathan Mark P. Brynildsen Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide Frontiers in Physiology Escherichia coli Hmp flavohemoglobin NO respiration bacteriostatic |
author_facet |
Darshan M. Sivaloganathan Mark P. Brynildsen |
author_sort |
Darshan M. Sivaloganathan |
title |
Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide |
title_short |
Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide |
title_full |
Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide |
title_fullStr |
Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide |
title_full_unstemmed |
Quantitative Modeling Extends the Antibacterial Activity of Nitric Oxide |
title_sort |
quantitative modeling extends the antibacterial activity of nitric oxide |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-04-01 |
description |
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. |
topic |
Escherichia coli Hmp flavohemoglobin NO respiration bacteriostatic |
url |
https://www.frontiersin.org/article/10.3389/fphys.2020.00330/full |
work_keys_str_mv |
AT darshanmsivaloganathan quantitativemodelingextendstheantibacterialactivityofnitricoxide AT markpbrynildsen quantitativemodelingextendstheantibacterialactivityofnitricoxide |
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