title: Antimicrobial and biophysical properties of surfactant supplemented with an antimicrobial peptide for treatment of bacterial pneumonia.
abstract: Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.
authors.affiliation: Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada bbanasch@uwo.ca.
authors.forename: Brandon J H
authors.initials: BJ
authors.lastname: Banaschewski
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Edwin J A
authors.initials: EJ
authors.lastname: Veldhuizen
authors.affiliation: Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Keating
authors.affiliation: Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Henk P
authors.initials: HP
authors.lastname: Haagsman
authors.affiliation: Department of Mechanical Engineering, University of Hawaii at Manoa, Honolulu, Hawaii, USA.
authors.forename: Yi Y
authors.initials: YY
authors.lastname: Zuo
authors.affiliation: Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada Department of Medicine, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Yamashita
authors.affiliation: Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada Department of Medicine, The University of Western Ontario, London, Ontario, Canada Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D002417:Cattle; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D011663:Pulmonary Surfactants