Abstract

Flavones are a class of natural plant secondary metabolites that have anti-inflammatory and anti-bacterial effects. Some flavones also activate the T2R14 bitter taste receptor, which is expressed in motile cilia of the sinonasal epithelium and activates innate immune nitric oxide (NO) production. Flavones may thus be potential therapeutics for respiratory infections. Our objective was to examine the anti-microbial effects of flavones on the common sinonasal pathogens Candida albicans, Staphylococcus aureus, and Pseudomonas aeruginosa, evaluating both planktonic and biofilm growth. Flavones had only very low-level antibacterial activity alone. They did not reduce biofilm formation, but did reduce production of the important P. aeruginosa inflammatory mediator and ciliotoxin pyocyanin. However, flavones exhibited synergy against P. aeruginosa in the presence of antibiotics or recombinant human lysozyme. They also enhanced the efficacy of antimicrobials secreted by cultured and primary human airway cells grown at air-liquid interface. This suggests that flavones may have anti-gram-negative potential as topical therapeutics when combined with antibiotics or in the context of innate antimicrobials secreted by the respiratory or other epithelia. This may have an additive effect when combined with T2R14-activated NO production. Additional studies are necessary to understand which flavone compounds or mixtures are the most efficacious.

Highlights

  • Chronic rhinosinusitis (CRS) is a syndrome of chronic inflammation and/or infection of the upper respiratory tract, which leads to substantial decreases in patient quality of life, creates >8 billion dollars in direct healthcare costs in the US alone, and can seed lower respiratory infections and exacerbate lung diseases [1,2,3]

  • We recently demonstrated that several flavones activate the bitter taste receptor isoform T2R14, which is expressed in sinonasal motile cilia [32]

  • We found that flavones likewise had only small effects on the growth of two coagulase– negative Staphylococcus (CNS) and two methicillin-resistant S. aureus (MRSA) clinical isolate strains (S2 Fig)

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Summary

Introduction

Chronic rhinosinusitis (CRS) is a syndrome of chronic inflammation and/or infection of the upper respiratory tract (nose and sinuses, termed the sinonasal cavity), which leads to substantial decreases in patient quality of life, creates >8 billion dollars in direct healthcare costs in the US alone, and can seed lower respiratory infections and exacerbate lung diseases [1,2,3]. CRS is an important public health concern, as it accounts for ~20% of antibiotic prescriptions in adults in the US [1, 4,5,6,7,8], making it a significant driver for the emergence of antibiotic

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