Activity of innate antimicrobial peptides and ivacaftor against clinical cystic fibrosis respiratory pathogens

Joanna E Payne, Alice V Dubois, Rebecca J Ingram, Sinead Weldon, Clifford C Taggart, J Stuart Elborn, Michael M Tunney

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There is a clear need for new antimicrobials to improve current treatment of chronic lung infection in people with cystic fibrosis (CF). This study determined the activities of antimicrobial peptides (AMPs) and ivacaftor, a novel CF transmembrane conductance regulator potentiator, for CF treatment. Antimicrobial activities of AMPs [LL37, human β-defensins (HβD) 1-4 and SLPI] and ivacaftor against clinical respiratory isolates (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus spp., Achromobacter spp. and Stenotrophomonas maltophilia) were determined using radial diffusion and time-kill assays, respectively. Synergy of LL37 and ivacaftor with tobramycin was determined by time-kill, with in vivo activity of ivacaftor and tobramycin compared using a murine infection model. LL37 and HβD3 were the most active AMPs tested, with MICs ranging from 3.2- ≥ 200 mg/L and 4.8- ≥ 200 mg/L, respectively, except for Achromobacter that was resistant. HβD1 and SLPI demonstrated no antimicrobial activity. LL37 demonstrated synergy with tobramycin against 4/5 S. aureus and 2/5 Streptococcus spp. isolates. Ivacaftor demonstrated bactericidal activity against Streptococcus spp. (mean log10 decrease 3.31 CFU/mL) and bacteriostatic activity against S. aureus (mean log10 change 0.13 CFU/mL), but no activity against other genera. Moreover, ivacaftor demonstrated synergy with tobramycin, with mean log10 decreases of 5.72 CFU/mL and 5.53 CFU/mL at 24 h for S. aureus and Streptococcus spp., respectively. Ivacaftor demonstrated immunomodulatory but no antimicrobial activity in a P. aeruginosa in vivo murine infection model. Following further modulation to enhance activity, AMPs and ivacaftor offer real potential as therapeutics to augment antibiotic therapy of respiratory infection in CF.

Original languageEnglish
Pages (from-to)427-435
JournalInternational Journal of Antimicrobial Agents
Issue number3
Early online date27 Jun 2017
Publication statusPublished - 01 Sept 2017


  • Journal Article


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