Department of Biomedical Sciences, Chosun University, Gwangju, Republic of Korea.
Department of Biomedical Sciences, Chosun University, Gwangju, Republic of Korea; Research Center for Proteineous Materials (RCPM), Chosun University, Gwangju, Republic of Korea.
Int J Antimicrob Agents. 2024 Feb;63(2):107054. doi: 10.1016/j.ijantimicag.2023.107054. Epub 2023 Dec 10.
The emergence of multidrug-resistant (MDR) Klebsiella pneumoniae strains causes severe problems in the treatment of bacterial infections owing to limited treatment options. Especially, carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly spreading worldwide and is emerging as a new cause of drug-resistant healthcare-associated infections. CRKP also has been announced by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) as one of the most pressing antibiotic resistance threats. Antimicrobial peptides (AMPs) are drawing considerable attention as ideal antibiotic alternative candidates to combat MDR bacterial infections. In a previous study, Osmin is composed of 17 amino acids and is isolated from solitary bee (Osmia rufa) venom. Herein, we evaluated the potential of Osmin to be used against drug-resistant K. pneumoniae as an alternative to conventional antibiotics. Osmin exhibited significant antimicrobial and anti-biofilm activity and lower toxicity than melittin, a well-known bee venom peptide. Additionally, we confirmed that it possesses a bactericidal mechanism that rapidly destroys bacterial membranes. Osmin was relatively more stable than melittin under the influence of various environmental factors and unlike conventional antibiotics, it exhibited a low bacterial resistance risk. During in vivo tests, Osmin reduced bacterial growth and the expression of pro-inflammatory cytokines and fibrosis-related genes in mice with CRKP-induced sepsis. Overall, our results indicate a high potential for Osmin to be used as a valuable therapeutic agent against drug-resistant K. pneumoniae infections.
多药耐药(MDR)肺炎克雷伯菌菌株的出现给细菌感染的治疗带来了严重问题,因为治疗选择有限。特别是,碳青霉烯类耐药肺炎克雷伯菌(CRKP)在全球范围内迅速传播,并且正在成为新的耐药性医疗保健相关感染的原因。美国疾病控制与预防中心(CDC)和世界卫生组织(WHO)也宣布 CRKP 是最紧迫的抗生素耐药威胁之一。抗菌肽(AMPs)作为对抗 MDR 细菌感染的理想抗生素替代候选物引起了相当大的关注。在之前的一项研究中,Osmin 由 17 个氨基酸组成,从独居蜜蜂(Osmia rufa)毒液中分离出来。在此,我们评估了 Osmin 作为传统抗生素的替代品,用于对抗耐药性肺炎克雷伯菌的潜力。Osmin 表现出显著的抗菌和抗生物膜活性,并且比众所周知的蜜蜂毒液肽 melittin 的毒性更低。此外,我们证实它具有一种杀菌机制,可以迅速破坏细菌膜。与 melittin 相比,Osmin 在各种环境因素的影响下相对更稳定,并且与传统抗生素不同,它表现出低细菌耐药风险。在体内试验中,Osmin 减少了 CRKP 诱导的败血症小鼠中的细菌生长和促炎细胞因子及纤维化相关基因的表达。总体而言,我们的结果表明 Osmin 具有很大的潜力,可以作为一种有价值的治疗药物,用于治疗耐药性肺炎克雷伯菌感染。