Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood <i>in vitro</i>.
Scheid. Annette A; Li. Ning N; Jeffers. Carleen C; Borriello. Francesco F; Joshi. Sweta S; Ozonoff. Al A; Pettengill. Matthew M; Levy. Ofer O
Key Findings
- LL‑37 (15 µg/ml) significantly boosted killing of Staph aureus, Staph epidermidis, and Candida albicans in term cord blood.
- In pre‑term cord blood, LL‑37 improved killing of Staph epidermidis and Candida albicans, but not Staph aureus.
- Recombinant mannose‑binding lectin showed only modest antifungal activity and only in term samples with already high baseline MBL levels.
Practical Outcomes
- For biohackers, the data confirms that LL‑37 has strong broad‑spectrum antimicrobial properties in a blood‑like environment, supporting its potential as a therapeutic agent. However, the work is limited to in‑vitro newborn blood, so it doesn’t give direct dosing or safety guidance for adult self‑use. The findings suggest that any future protocols involving LL‑37 should consider the age of the host and the specific pathogen targeted.
Summary
The study shows that adding the antimicrobial peptide LL‑37 to newborn cord blood in the lab makes the blood better at killing common bacteria (Staph aureus, Staph epidermidis) and a fungus (Candida albicans). This effect was seen in both full‑term and pre‑term blood, while a similar protein called mannose‑binding lectin only helped a little against the fungus in some cases.
Abstract
<b>Background:</b> There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. <b>Methods:</b> The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12-14) against <i>Staphylococcus aureus</i> (SA) USA 300 (2x10 <sup>4</sup> CFU/ml), <i>Staphylococcus epidermis</i> (SE) 1457 (2x10 <sup>4</sup> CFU/ml) and <i>Candida albicans</i> (CA) SC5314 (1x10 <sup>4</sup> CFU/ml). After incubation (1, 45, or 180 min), CFUs were enumerated by plating blood onto agar plates. Supernatants were collected for measurement of MBL via ELISA. <b>Results:</b> Preterm cord blood demonstrated impaired endogenous killing capacity against SA and SE compared to term blood. Addition of LL-37 strongly enhanced antimicrobial/antifungal activity vs SA, SE and CA in term blood and SE and CA in preterm blood. By contrast, rMBL showed modest fungistatic activity vs CA in a sub-analysis of term newborns with high basal MBL levels. Baseline MBL levels varied within preterm and term cohorts with no correlation to gestational age. In summary, exogenous LL-37 demonstrated significant antimicrobial activity against SA, SE and CA in term and SE and CA in preterm human blood tested <i>in vitro</i>. rMBL demonstrated modest antifungal activity in term cord blood of individuals with high baseline MBL levels. <b>Conclusions:</b> To the extent that our <i>in vitro</i> results predict the effects of APPs <i>in vivo</i>, development of APPs for prevention and treatment of infection should take into account host age as well as the target pathogen.
Study Information
pubmed
2018
2018-05-21T00:00:00.000Z
10.12688/f1000research.14736.1
6
30