@article{087fbe4b41574abcb60dc820e2a7bfe1,
title = "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.",
keywords = "Escherichia coli, Hmp, NO, bacteriostatic, flavohemoglobin, respiration",
author = "Sivaloganathan, {Darshan M.} and Brynildsen, {Mark P.}",
note = "Funding Information: We thank Wen Kang Chou and Xuanqing (Mike) Wan for assistance. Parameter optimizations were performed using the Terascale Infrastructure for Groundbreaking Research in Science and Engineering (TIGRESS) high performance computer center at Princeton University, which is jointly supported by the Princeton Institute for Computational Science and Engineering (PICSciE) and the Princeton University Office of Information Technology{\textquoteright}s Research Computing department. Funding Information: We thank Wen Kang Chou and Xuanqing (Mike) Wan for assistance. Parameter optimizations were performed using the Terascale Infrastructure for Groundbreaking Research in Science and Engineering (TIGRESS) high performance computer center at Princeton University, which is jointly supported by the Princeton Institute for Computational Science and Engineering (PICSciE) and the Princeton University Office of Information Technology?s Research Computing department. Funding. This work was supported by the National Science Foundation (CBET-1453325), the Natural Sciences and Engineering Research Council of Canada (NSERC), and Princeton University (Helen Shipley Hunt Fund and Forese Family Fund for Innovation). Funding Information: This work was supported by the National Science Foundation (CBET-1453325), the Natural Sciences and Engineering Research Council of Canada (NSERC), and Princeton University (Helen Shipley Hunt Fund and Forese Family Fund for Innovation). Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Sivaloganathan and Brynildsen.",
year = "2020",
month = apr,
day = "17",
doi = "10.3389/fphys.2020.00330",
language = "English (US)",
volume = "11",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Research Foundation",
}