DNase-mediated eDNA removal enhances D-LL-31 activity against biofilms of bacteria isolated from chronic rhinosinusitis patients

Chronic rhinosinusitis (CRS) is a chronic infection of the nasal cavity and paranasal sinuses associated with the presence of a microbial biofilm. Extracellular DNA (eDNA) is an important component of the biofilm matrix. Antimicrobial peptides (AMPs) are natural peptides with the ability to kill mic...

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Bibliographic Details
Published in:Biofouling (Chur, Switzerland) Switzerland), 2020-12, Vol.36 (9), p.1117-1128
Main Authors: Wongkaewkhiaw, Saharut, Kanthawong, Sakawrat, Bolscher, Jan G. M., Nazmi, Kamran, Taweechaisupapong, Suwimol, Krom, Bastiaan P.
Format: Article
Language:English
Subjects:
AMP
Anti-Bacterial Agents
Antiinfectives and antibacterials
Antimicrobial activity
Antimicrobial agents
Antimicrobial peptides
Bacteria - genetics
Bactericidal activity
Biofilms
Chronic infection
chronic rhinosinusitis
D-enantiomer peptide
D-LL-31
Deoxyribonuclease
Deoxyribonuclease I
Deoxyribonucleases
Deoxyribonucleic acid
Disease resistance
Dispersal
DNA
DNase I
eDNA
Environmental DNA
Extracellular
Incubation period
Microorganisms
Nose
Paranasal sinuses
Peptides
Proteolysis
Rhinosinusitis
Sinus
Sinuses
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Summary:Chronic rhinosinusitis (CRS) is a chronic infection of the nasal cavity and paranasal sinuses associated with the presence of a microbial biofilm. Extracellular DNA (eDNA) is an important component of the biofilm matrix. Antimicrobial peptides (AMPs) are natural peptides with the ability to kill microorganisms. D-LL-31 is a synthetic variant of the AMP cathelicidin with increased resistance to proteolytic breakdown. In this study it is shown for 3 clinical CRS isolates that treatment of 24 h biofilms with DNase I enhanced the antimicrobial activity of D-LL-31. Conversely, co-incubation of D-LL-31 at the IC 50 value with exogenous DNA resulted in reduced antimicrobial activity. DNase I alone did not show antimicrobial activity against the isolates tested but caused dispersal of an established biofilm. Hence, the presence of eDNA in the biofilm matrix reduced AMP-mediated killing. These results suggest that combination therapy with proteolysis resistant AMP D-LL-31 and DNase could be considered for effective treatment of CRS.
ISSN:0892-7014
1029-2454
DOI:10.1080/08927014.2020.1857741