TY - JOUR
T1 - Eradication of staphylococcus aureus biofilm infections using synthetic antimicrobial peptides
AU - Zapotoczna, Marta
AU - Forde, Éanna
AU - Hogan, Siobhan
AU - Humphreys, Hilary
AU - O'gara, James P.
AU - Fitzgerald-Hughes, Deirdre
AU - Devocelle, Marc
AU - O'Neill, Eoghan
N1 - Publisher Copyright:
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2017/3/15
Y1 - 2017/3/15
N2 - Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.
AB - Here, we demonstrate that antimicrobial peptides (AMPs) are an effective antibiofilm treatment when applied as catheter lock solutions (CLSs) against S. aureus biofilm infections. The activity of synthetic AMPs (Bac8c, HB43, P18, Omiganan, WMR, Ranalexin, and Polyphemusin) was measured against early and mature biofilms produced by methicillin-resistant S. aureus and methicillin-susceptible S. aureus isolates from patients with device-related infections grown under in vivo-relevant biofilm conditions. The cytotoxic and hemolytic activities of the AMPs against human cells and their immunomodulatory potential in human blood were also characterized. The D-Bac8c2,5Leu variant emerged as the most effective AMP during in vitro studies and was also highly effective in eradicating S. aureus biofilm infection when used in a CLS rat central venous catheter infection model. These data support the potential use of D-Bac8c2,5Leu, alone or in combination with other AMPs, in the treatment of S. aureus intravenous catheter infections.
KW - Antimicrobial peptides (AMPs)
KW - Biofilm
KW - Catheter lock solution (CLS)
KW - Staphylococcus aureus
UR - https://www.scopus.com/pages/publications/85019683918
U2 - 10.1093/infdis/jix062
DO - 10.1093/infdis/jix062
M3 - Article
SN - 0022-1899
VL - 215
SP - 975
EP - 983
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -