Song Yun-Qi, Kyung Su Min, Kim Suji, Kim Gun, Lee So Yeong, Yoo Han Sang
Department of Infectious Disease, Seoul National University , Seoul, Republic of Korea.
Research Institute for Veterinary Science, Seoul National University , Seoul, Republic of Korea.
Microbiol Spectr. 2023 Aug 9;11(5):e0043023. doi: 10.1128/spectrum.00430-23.
is a common bacterium in nosocomial infection. The biofilm-forming ability and antimicrobial resistance make biofilm infection refractory to patients requiring hospitalization, especially patients in the intensive care unit. Therefore, many alternative compounds have been developed. A newly synthesized peptide, RP557, derived from human cathelicidin LL-37, was evaluated for its antimicrobial and antibiofilm effect toward carbapenem-resistant (CRPA). The results showed that regardless of the resistance to carbapenems, the minimal inhibition concentrations of RP557 and LL-37 against were 32 µg/mL and 256 µg/mL, respectively. Both RP557 and LL-37 significantly reduced the biofilm mass at subMICs, while subMICs of carbapenems induced biofilm formation. RP557 could also remove approximately 50% of the mature biofilm at a concentration of 64 µg/mL, while 256 µg/mL LL-37 was needed to remove it. A quarter MIC of RP557 and LL-37 was used together with carbapenems (ertapenem, imipenem, and meropenem). The results show that both RP-557 and LL-37 might increase the susceptibility to CRPA by 4-16 times. Significant gene expression level changes were observed in RP557- or LL-37-treated CRPA. Confocal images showed that biofilm structures and biofilm cell viability were significantly reduced in the LL-37- or RP557-treated groups. Therefore, RP557 and its structural origin, LL-37, could be potential treatments for carbapenem-resistant infection, especially for chronic biofilm infection. IMPORTANCE is one of the major pathogens of nosocomial infection. Combined its biofilm-forming ability with carbapenem-resistance, it is hard to handle infection, especially for patients requiring hospitalization. Antimicrobial peptide is a type of potential compound for bacterial infection treatment. Among these, RP557 was found effective in inhibiting biofilm previously. By assessing its effect on both carbapenem-resistant planktonic cells and biofilm, our results offered a potential treatment for carbapenem-resistant infection. It could be helpful to treat severe nosocomial infection related to carbapenem-resistant bacteria and increase the patients' survival rate.
是医院感染中常见的一种细菌。其形成生物膜的能力和抗菌耐药性使得生物膜感染对于需要住院治疗的患者,尤其是重症监护病房的患者来说难以治愈。因此,人们开发了许多替代化合物。一种新合成的源自人cathelicidin LL-37的肽RP557,针对耐碳青霉烯类肺炎克雷伯菌(CRPA)进行了抗菌和抗生物膜效果评估。结果表明,无论对碳青霉烯类药物的耐药情况如何,RP557和LL-37对其的最低抑菌浓度分别为32 µg/mL和256 µg/mL。RP557和LL-37在低于最低抑菌浓度时均能显著降低生物膜量,而碳青霉烯类药物的低于最低抑菌浓度时会诱导生物膜形成。RP557在浓度为64 µg/mL时还能去除约50%的成熟生物膜,而去除它则需要256 µg/mL的LL-37。将RP557和LL-37的四分之一最低抑菌浓度与碳青霉烯类药物(厄他培南、亚胺培南和美罗培南)联合使用。结果表明,RP-557和LL-37都可能使对CRPA的敏感性提高4至16倍。在经RP557或LL-37处理的CRPA中观察到显著的基因表达水平变化。共聚焦图像显示,在经LL-37或RP557处理的组中,生物膜结构和生物膜细胞活力显著降低。因此,RP557及其结构来源LL-37可能是耐碳青霉烯类感染,尤其是慢性生物膜感染的潜在治疗方法。重要性肺炎克雷伯菌是医院感染的主要病原体之一。结合其形成生物膜的能力和对碳青霉烯类药物的耐药性,肺炎克雷伯菌感染很难处理,尤其是对于需要住院治疗的患者。抗菌肽是一类用于治疗细菌感染的潜在化合物。其中,RP557此前被发现对抑制生物膜有效。通过评估其对耐碳青霉烯类肺炎克雷伯菌浮游细胞和生物膜的作用,我们的结果为耐碳青霉烯类感染提供了一种潜在的治疗方法。这可能有助于治疗与耐碳青霉烯类细菌相关的严重医院感染并提高患者的生存率。