Antimicrobial and biophysical properties of surfactant supplemented with an antimicrobial peptide for treatment of bacterial pneumonia.
Banaschewski. Brandon J H BJ; Veldhuizen. Edwin J A EJ; Keating. Eleonora E; Haagsman. Henk P HP; Zuo. Yi Y YY; Yamashita. Cory M CM; Veldhuizen. Ruud A W RA
Key Findings
- Adding antimicrobial peptides to surfactant increased its spreading ability compared to surfactant alone.
- The CATH‑2 peptide retained the most bactericidal activity when mixed with surfactant; LL‑37 showed less benefit.
- Surfactant‑peptide mixtures did not significantly worsen the surfactant’s surface tension, an important lung function.
Practical Outcomes
- At this point there’s no ready‑to‑use protocol for biohackers. The work suggests that delivering AMPs via lung surfactant could be a future strategy, but more animal studies are needed before anyone should try it on themselves.
Summary
Researchers tested mixing lung surfactant with several antimicrobial peptides, including LL‑37, to see if the combo could still spread well in the lungs and kill drug‑resistant bacteria. While all mixes spread better than surfactant alone, the peptide CATH‑2 kept the strongest antibacterial effect; LL‑37 didn’t stand out. The study is still in test‑tube (in‑vitro) stage and needs animal testing before any real‑world use.
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.
Study Information
pubmed
2015
2015-03-09T00:00:00.000Z
10.1128/aac.04937-14