(525) Antimicrobial peptides and filamentous bacteriophages have opposing effects on sputum antibiotic penetration

Background: Chronic Pseudomonas aeruginosa infections pose a major challenge to cystic fibrosis (CF) patients due to sputum biofilm production and antibiotic tolerance. We have investigated the host and microbial factors that contribute to these effects.P. aeruginosa produces a filamentous bacteriophage called Pf which acts as a structural element in P aeruginosa biofilms and promotes antibiotic tolerance.

Methods: Fluorescent microscopy and enthalphic interactions are used to investigate the effects of phage and polymer on antibiotics diffusion.

Results: Complexes of Pf phage and sputum polymers bind tobramycin via enthalphic interactions that prevent antibiotic diffusion. Conversely, LL-37 (cathelicidin), an antimicrobial peptide that is abundant in the sputum of healthy individuals, disrupts these interactions. LL-37 thereby enhances antibiotic penetration of sputum biofilms, and increase the bacterial killing efficacy of tobramycin treatment.

Conclusions: Together, these studies indicate that the balance between LL-37 and Pf phage impacts sputum antibiotic tolerance and suggests. It may be possible to promote the activity of inhaled antibiotics using LL-37.

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