PepBiotics, novel cathelicidin-inspired antimicrobials to fight pulmonary bacterial infections.
Biochim Biophys Acta Gen Subj
; 1865(9): 129951, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34147544
ABSTRACT
BACKGROUND:
Antimicrobial peptides are considered potential alternatives to antibiotics. Here we describe the antibacterial properties of a family of novel cathelicidin-related (CR-) peptides, which we named PepBiotics, against bacteria typically present in cystic fibrosis (CF) patients.METHODS:
Broth dilution assays were used to determine antibacterial activity of PepBiotics under physiological conditions, as well as development of bacterial resistance against these peptides. Toxicity was tested in mice and cell cultures while molecular interactions of PepBiotics with bacterial membrane components was determined using CD, ITC and LPS/LTA induced macrophage studies.RESULTS:
A relatively small number of PepBiotics remained highly antibacterial against CF-related respiratory pathogens Pseudomonas aeruginosa and Staphylococcus aureus, at high ionic strength and low pH. Interestingly, these PepBiotics also prevented LPS/LTA induced activation of macrophages and was shown to be non-toxic to primary human nasal epithelial cells. Furthermore, both P. aeruginosa and S. aureus were unable to induce resistance against CR-163 and CR-172, two PepBiotics selected for their excellent antimicrobial and immunomodulatory properties. Toxicity studies in mice indicated that intratracheal administration of CR-163 was well tolerated in vivo. Finally, interaction of CR-163 with bacterial-type anionic membranes but not with mammalian-type (zwitterionic lipid) membranes was confirmed using ITC and 31P solid state NMR.CONCLUSIONS:
PepBiotics are a promising novel class of highly active antimicrobial peptides, of which CR-163 showed the most potential for treatment of clinically relevant (CF-) pathogens in physiological conditions. GENERALSIGNIFICANCE:
These observations emphasize the therapeutic potential of PepBiotics against CF-related bacterial respiratory infections.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pseudomonas aeruginosa
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Staphylococcus aureus
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Infecciones Bacterianas
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Péptidos Catiónicos Antimicrobianos
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Antibacterianos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochim Biophys Acta Gen Subj
Año:
2021
Tipo del documento:
Article
País de afiliación:
Países Bajos