Abstract

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 IC₅₀ 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.

摘要

慢性鼻-鼻窦炎（CRS）是与微生物生物膜有关的鼻腔和鼻旁窦的慢性感染。细胞外DNA（eDNA）是生物膜基质的重要组成部分。抗菌肽（AMPs）是具有杀死微生物能力的天然肽。D-LL-31是AMP cathelicidin的合成变体，对蛋白水解破坏的抵抗力增强。在这项研究中，对于3种临床CRS分离株表明，用DNase I处理24 h生物膜可增强D-LL-31的抗菌活性。相反，在IC _50上共同孵育D-LL-31外源DNA的抗微生物活性降低。单独的DNase I并未显示出对测试分离物的抗菌活性，但引起了已建立的生物膜的分散。因此，生物膜基质中eDNA的存在减少了AMP介导的杀伤。这些结果表明，可以考虑将抗蛋白水解的AMP D-LL-31和DNase联合使用以有效治疗CRS。