D-LL-31 enhances biofilm-eradicating effect of currently used antibiotics for chronic rhinosinusitis and its immunomodulatory activity on human lung epithelial cells.
A549 Cells
Adolescent
Adult
Aged
Anti-Bacterial Agents
/ pharmacology
Antimicrobial Cationic Peptides
/ pharmacology
Bacteria
/ growth & development
Bacterial Physiological Phenomena
/ drug effects
Biofilms
/ drug effects
Chronic Disease
Epithelial Cells
/ metabolism
Female
Humans
Lung
/ metabolism
Male
Middle Aged
Rhinitis
/ drug therapy
Sinusitis
/ drug therapy
Cathelicidins
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
06
2020
accepted:
18
11
2020
entrez:
16
12
2020
pubmed:
17
12
2020
medline:
20
1
2021
Statut:
epublish
Résumé
Chronic rhinosinusitis (CRS) is a chronic disease that involves long-term inflammation of the nasal cavity and paranasal sinuses. Bacterial biofilms present on the sinus mucosa of certain patients reportedly exhibit resistance against traditional antibiotics, as evidenced by relapse, resulting in severe disease. The aim of this study was to determine the killing activity of human cathelicidin antimicrobial peptides (LL-37, LL-31) and their D-enantiomers (D-LL-37, D-LL-31), alone and in combination with conventional antibiotics (amoxicillin; AMX and tobramycin; TOB), against bacteria grown as biofilm, and to investigate the biological activities of the peptides on human lung epithelial cells. D-LL-31 was the most effective peptide against bacteria under biofilm-stimulating conditions based on IC50 values. The synergistic effect of D-LL-31 with AMX and TOB decreased the IC50 values of antibiotics by 16-fold and could eliminate the biofilm matrix in all tested bacterial strains. D-LL-31 did not cause cytotoxic effects in A549 cells at 25 μM after 24 h of incubation. Moreover, a cytokine array indicated that there was no significant induction of the cytokines involving in immunopathogenesis of CRS in the presence of D-LL-31. However, a tissue-remodeling-associated protein was observed that may prevent the progression of nasal polyposis in CRS patients. Therefore, a combination of D-LL-31 with AMX or TOB may improve the efficacy of currently used antibiotics to kill biofilm-embedded bacteria and eliminate the biofilm matrix. This combination might be clinically applicable for treatment of patients with biofilm-associated CRS.
Identifiants
pubmed: 33326455
doi: 10.1371/journal.pone.0243315
pii: PONE-D-20-18804
pmc: PMC7743948
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antimicrobial Cationic Peptides
0
Cathelicidins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0243315Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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