Activity of Abundant Antimicrobials of the Human Airway

Abstract

Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing infection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of the CF airway. We found that abundant airway antimicrobial factors kill common CF pathogens, although Burkholderia was relatively resistant. To study the antibacterial activity, we developed a rapid, sensitive, and quantitative in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inhibited by high ionic strength, and it was particularly sensitive to divalent cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be partially compensated by increased concentrations of antibacterial factors, thus there was no one unique salt concentration for inhibition. CF airway secretions also contain abundant mucin and elastase; however, these had no effect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fluids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results suggest approaches toward developing treatments aimed at preventing or reducing airway infections in individuals with CF.

pH modulates the activity and synergism of the airway surface liquid antimicrobials β-defensin-3 and LL-37

“…In the mammalian respiratory system, the interface between the environment and the organism is a thin layer of airway surface liquid (ASL). To maintain sterile lungs and protect against bombardment with bacteria, mammalian lungs have evolved multiple protective mechanisms, one of which is antimicrobials in ASL that rapidly kill inhaled and aspirated bacteria (5)(6)(7)(8)(9).…”

“…To assay bacterial viability, we used an S. aureus strain that expresses a bacterial luciferase (S. aureus Xen29) (49); the bioluminescence is energy-dependent, and light output correlates well with counts of colony-forming units (8). To avoid confounding effects arising from bacterial growth, we used minimal bacterial growth conditions-1% tryptic soy broth (TSB) medium (8). By assaying light output, we were able to obtain realtime measurements of microbial viability in a 96-well plate format.…”

ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU

“…[7][8][9][10][11] Many nosocomial infections in the NICU are with organisms that are of very low virulence in healthy adults, such as C. albicans and coagulasenegative staphylococcus. 21 A low IgG concentration is one factor predisposing preterm neonates to these infections, 22 and disruption of the mucosal barrier by the presence of tubes in the trachea, nose or mouth is likely another predisposing factor.…”

“…6 One problem with using saline for periodic upper airway care in a neonate is that high concentrations of sodium and chloride inactivate natural antimicrobial properties of airway secretions. [7][8][9][10][11][12][13] Tracheal secretions, nasal secretions and saliva all have very low concentrations of sodium and chloride. Moreover, those secretions contain potent natural antibacterial substances that are inhibited by saline.…”

Dinámica y patología del barrido mucociliar como mecanismo defensivo del pulmón y alternativas farmacológicas de tratamiento

“…Alberga moléculas con actividad antibacteriana, antifúngica y antiviral como lisozima, lactoferrina, siderocalina, lactoperoxidasa y defensinas, facilitando la acción de macrófagos epiteliales 17,18 . Su espesor de entre 5 y 10 μm es crítico ya que permite la función de los cilios que miden 6 a 7 μm.…”