Elsevier

Redox Biology

Volume 39, February 2021, 101826
Redox Biology

Research Paper
Antimicrobial effects of nitric oxide in murine models of Klebsiella pneumonia

https://doi.org/10.1016/j.redox.2020.101826Get rights and content
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Highlights

  • Nitric oxide inhalation reduces viable Klebsiella pneumoniae in lung tissue.

  • Nitric oxide improves survival rates in murine Klebsiella pneumonia.

  • Exposure to nitric oxide leads to Klebsiella cell wall degradation in-vitro.

  • Nitric oxide is antibacterial against multiple drug resistant Klebsiella in-vitro.

Abstract

Rationale

Inhalation of nitric oxide (NO) exerts selective pulmonary vasodilation. Nitric oxide also has an antimicrobial effect on a broad spectrum of pathogenic viruses, bacteria and fungi.

Objectives

The aim of this study was to investigate the effect of inhaled NO on bacterial burden and disease outcome in a murine model of Klebsiella pneumonia.

Methods

Mice were infected with Klebsiella pneumoniae and inhaled either air alone, air mixed with constant levels of NO (at 80, 160, or 200 parts per million (ppm)) or air intermittently mixed with high dose NO (300 ppm). Forty-eight hours after airway inoculation, the number of viable bacteria in lung, spleen and blood was determined. The extent of infiltration of the lungs by inflammatory cells and the level of myeloperoxidase activity in the lungs were measured. Atomic force microscopy was used to investigate a possible mechanism by which nitric oxide exerts a bactericidal effect.

Measurements and main results

Compared to control animals infected with K. pneumoniae and breathed air alone, intermittent breathing of NO (300 ppm) reduced viable bacterial counts in lung and spleen tissue. Inhaled NO reduced infection-induced lung inflammation and improved overall survival of mice. NO destroyed the cell wall of K. pneumoniae and killed multiple-drug resistant K. pneumoniae in-vitro.

Conclusions

Intermittent administration of high dose NO may be an effective approach to the treatment of pneumonia caused by K. pneumoniae.

Keywords

Lung inflammation
Treatment
Bactericidal
Outcome

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contributed equally.