Reddersen Kirsten, Greber Katarzyna E, Korona-Glowniak Izabela, Wiegand Cornelia
Klinik für Hautkrankheiten, Universitätsklinikum Jena, 07743 Jena, Germany.
Physical Chemistry Department, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland.
Antibiotics (Basel). 2020 Dec 8;9(12):879. doi: 10.3390/antibiotics9120879.
The search for new antimicrobial strategies is of major importance since there is a growing resistance of both bacteria and fungi to existing antimicrobials. Lipopeptides are promising and potent antimicrobial compounds. For translation into clinically useful molecules, effectiveness of peptide treatment against human infections must be proved in complex in vitro wound models. The aim of this study was to examine if the synthesized short lipopeptides (C)-KKKK-NH and (C)-KKKK-NH can protect HaCaT keratinocytes from bacterial damage caused by infection in a coculture model. After 1 h, 24 h, and 48 h incubation, cellular ATP level and release of the cytotoxicity marker LDH as well as the proinflammatory cytokines interleukin-6 and interleukin-1α were measured. Infection of the keratinocytes resulted in strong bacterial damage of HaCaT cells along with low cellular ATP levels and high release of LDH, IL-6, and IL-1α after 24 h and 48 h. Incubation of the infected human keratinocytes with (C)-KKKK-NH and (C)-KKKK-NH resulted in protection of the keratinocytes from bacterial damage caused by infection with ATP, LDH, IL-6, and IL-1α levels comparable to the untreated control. Hence, both synthesized lipopeptides are promising candidates with high therapeutic potential in dermatology for the treatment of topical infections.
由于细菌和真菌对现有抗菌药物的耐药性不断增强，寻找新的抗菌策略至关重要。脂肽是有前景且强效的抗菌化合物。为了转化为临床上有用的分子，必须在复杂的体外伤口模型中证明肽治疗对人类感染的有效性。本研究的目的是在共培养模型中检验合成的短脂肽（C）-KKKK-NH和（C）-KKKK-NH是否能保护HaCaT角质形成细胞免受感染引起的细菌损伤。在孵育1小时、24小时和48小时后，测量细胞ATP水平、细胞毒性标志物LDH的释放以及促炎细胞因子白细胞介素-6和白细胞介素-1α。角质形成细胞感染导致HaCaT细胞在24小时和48小时后受到严重细菌损伤，同时细胞ATP水平较低，LDH、IL-6和IL-1α释放较高。用（C）-KKKK-NH和（C）-KKKK-NH孵育受感染的人类角质形成细胞可保护角质形成细胞免受感染引起的细菌损伤，ATP、LDH、IL-6和IL-1α水平与未处理的对照相当。因此，这两种合成脂肽都是皮肤病学中具有高治疗潜力的有前景的候选药物，可用于治疗局部感染。
