Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Biofouling. 2020 Oct;36(9):1117-1128. doi: 10.1080/08927014.2020.1857741. Epub 2020 Dec 9.
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 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.
慢性鼻-鼻窦炎（CRS）是一种鼻腔和鼻窦的慢性感染，与微生物生物膜的存在有关。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 是抗菌肽 cathelicidin 的一种合成变体，具有增强的抗蛋白水解破坏的能力。在这项研究中，对 3 株临床 CRS 分离株进行了研究，结果表明，用 DNA 酶 I 处理 24 小时生物膜可增强 D-LL-31 的抗菌活性。相反，将 D-LL-31 在 IC 值与外源性 DNA 共孵育会导致抗菌活性降低。DNA 酶 I 单独对测试的分离株没有抗菌活性，但会导致已建立的生物膜的分散。因此，生物膜基质中 eDNA 的存在降低了 AMP 介导的杀伤作用。这些结果表明，使用蛋白酶抗性 AMP D-LL-31 和 DNA 酶的联合治疗可能被认为是治疗 CRS 的有效方法。
