Relative susceptibility of airway organisms to antimicrobial effects of nitric oxide

呼吸道生物对一氧化氮抗菌作用的相对敏感性

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作者:Alan D Workman, Ryan M Carey, Michael A Kohanski, David W Kennedy, James N Palmer, Nithin D Adappa, Noam A Cohen

Background

Nitric oxide (NO) is released in the airway as a critical component of innate immune defense against invading pathogenic organisms. It is well documented that bacteriostatic and bactericidal effects of NO are concentration-dependent. However, few data exist comparing relative susceptibility of common pathogens to NO at physiologic concentrations. In this study we evaluated the effects of NO on 4 common airway bacteria and 1 fungus, and examined the potential implications of discrepancies in sensitivity.

Conclusion

Common airway pathogens have varying levels of susceptibility to NO at physiologic concentrations of innate immune defense. Relative sensitivity of P aeruginosa and relative resistance of S epidermis may help explain the composition of the healthy microbiome, as well as opportunistic infection in the absence of induced NO release.

Methods

Staphylococcus epidermis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans cultures were adjusted to a uniform optical density (OD) and grown in log phase at 37°C with varying concentrations of NO formed by DETA NONOate. Both OD readings and colony forming units (CFUs) were measured at varying time-points to evaluate for inhibitory effects of NO.

Results

P aeruginosa and C albicans were significantly more sensitive to NO at physiologic concentrations typical of the human airway. S aureus was attenuated by NO to a lesser degree, and K pneumoniae and S epidermis were more resistant to NO at all concentrations tested. Air surface liquid from cultured human sinonasal epithelial cells had an additive effect in bacterial killing of P aeruginosa, but not in S aureus.

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