Quantifying Nitric Oxide Flux Distributions

Sivaloganathan, Darshan M.; Wan, Xuanqing; Brynildsen, Mark P.

doi:10.1007/978-1-0716-0159-4_8

Cited by 3 publications

(2 citation statements)

References 47 publications

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“…Using this conversion rate, we created a plot with the concentration of NO produced on the x -axis and changes in current (ΔpA) on the y -axis, which was used to fit a line. The slope of the fitted equation was then used to convert current readings to NO concentration for experiments conducted on that day ( Sivaloganathan et al, 2020 ). In the cases when CFU/mL data were measured, 200 μL were removed from the bioreactor for plating every 30 min.…”

Section: Methodsmentioning

confidence: 99%

Synergy Screening Identifies a Compound That Selectively Enhances the Antibacterial Activity of Nitric Oxide

Chou

Vaikunthan

Schröder

et al. 2020

Front. Bioeng. Biotechnol.

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Antibiotic resistance poses a serious threat to global health. To reinforce the antiinfective arsenal, many novel therapeutic strategies to fight bacterial infections are being explored. Among them, anti-virulence therapies, which target pathways important for virulence, have attracted much attention. Nitric oxide (NO) defense systems have been identified as critical for the pathogenesis of various bacteria, making them an appealing therapeutic target. In this study, we performed chemical screens to identify inhibitors of NO detoxification in Escherichia coli. We found that 2-mercaptobenzothiazole (2-MBT) can potently inhibit cellular detoxification of NO, achieving a level of inhibition that resembled the effect of genetically removing Hmp, the dominant detoxification enzyme under oxygenated conditions. Further analysis revealed that in the presence of NO, 2-MBT impaired the catalysis of Hmp and synthesis of Hmp and other proteins, whereas in its absence there were minimal perturbations to growth and protein synthesis. In addition, by studying the structure-activity relationship of 2-MBT, we found that both sulfur atoms in 2-MBT were vital for its inhibition of NO detoxification. Interestingly, when 2-mercaptothiazole (2-MT), which lacked the benzene ring, was used, differing biological activities were observed, although they too were NO dependent. Specifically, 2-MT could still prohibit NO detoxification, though it did not interfere with Hmp catalysis; rather, it was a stronger inhibitor of protein synthesis and it reduced the transcript levels of hmp, which was not observed with 2-MBT. Overall, these results provide a strong foundation for further exploration of 2-MBT and 2-MT for therapeutic applications.

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Section: Methodsmentioning

confidence: 99%

Synergy Screening Identifies a Compound That Selectively Enhances the Antibacterial Activity of Nitric Oxide

Chou

Vaikunthan

Schröder

et al. 2020

Front. Bioeng. Biotechnol.

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“…1D by ~95% (and see below)), while starting with 60 µM DEA NONOate, NO exposure is reduced to 6 µM x 15 minutes, and the catalase inhibition is only ~50% (see below). NONOate donors are known to yield actual NO concentrations much lower than the initial donor concentrations (22,53,57,58).…”

Section: Parameters Of the H2o2+no Treatmentmentioning

confidence: 99%

Nitric oxide precipitates catastrophic chromosome fragmentation by bolstering both hydrogen peroxide and Fe(II) Fenton reactants in E. coli

Agashe

Kuzminov

2022

Journal of Biological Chemistry

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Pseudomonas aeruginosa prioritizes detoxification of hydrogen peroxide over nitric oxide

Sivaloganathan

Brynildsen

2021

BMC Res Notes

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Objective Bacteria are exposed to multiple concurrent antimicrobial stressors within phagosomes. Among the antimicrobials produced, hydrogen peroxide and nitric oxide are two of the most deleterious products. In a previous study, we discovered that when faced with both stressors simultaneously, Escherichia coli prioritized detoxification of hydrogen peroxide over nitric oxide. In this study, we investigated whether such a process was conserved in another bacterium, Pseudomonas aeruginosa. Results P. aeruginosa prioritized hydrogen peroxide detoxification in a dose-dependent manner. Specifically, hydrogen peroxide detoxification was unperturbed by the presence of nitric oxide, whereas larger doses of hydrogen peroxide produced longer delays in nitric oxide detoxification. Computational modelling revealed that the rate of nitric oxide consumption in co-treated cultures was biphasic, with cells entering the second phase of detoxification only after hydrogen peroxide was eliminated from the culture.

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Quantifying Nitric Oxide Flux Distributions

Cited by 3 publications

References 47 publications

Synergy Screening Identifies a Compound That Selectively Enhances the Antibacterial Activity of Nitric Oxide

Synergy Screening Identifies a Compound That Selectively Enhances the Antibacterial Activity of Nitric Oxide

Nitric oxide precipitates catastrophic chromosome fragmentation by bolstering both hydrogen peroxide and Fe(II) Fenton reactants in E. coli

Pseudomonas aeruginosa prioritizes detoxification of hydrogen peroxide over nitric oxide

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