School of Life Sciences, Tianjin University, Tianjin 300072, China.
Key Laboratory of Bioactive Peptides of Yunnan Province, National & Local Joint Engineering Center of Natural Bioactive Peptides, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Int J Mol Sci. 2023 Aug 30;24(17):13453. doi: 10.3390/ijms241713453.
() infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, gains a significant advantage over host defense mechanisms, with hypercoagulation induced by potentially aggravating infectious diseases. Recently, we and other researchers identified that a higher level of LL-37, one endogenous antimicrobial peptide with a significant killing effect on infection, resulted in thrombosis formation through the induction of platelet activation and potentiation of the coagulation factor enzymatic activity. In the current study, we identified a novel antimicrobial peptide (RK22) from the salivary gland transcriptome of () through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against , including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed by inhibiting biofilm formation and promoting biofilm eradication, with good plasma stability, negligible cytotoxicity, minimal hemolytic activity, and no significant promotion of the coagulation system. Notably, administration of RK22 significantly inhibited infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against infection.
()感染是发病率和死亡率的主要原因，而耐药性使情况更加复杂。通过操纵凝血系统，()获得了对抗宿主防御机制的显著优势，而()诱导的过度凝血可能使传染病恶化。最近，我们和其他研究人员发现，一种内源性抗菌肽 LL-37 的水平较高，对()感染有显著的杀伤作用，通过诱导血小板活化和增强凝血因子的酶活性，导致血栓形成。在本研究中，我们通过生物信息学分析从()的唾液腺转录组中鉴定出一种新型抗菌肽(RK22)，然后对其进行了合成，该肽对包括具有最小抑菌浓度 (MIC) 为 6.25 μg/mL 的临床耐药株在内的()表现出良好的抗菌活性。RK22 肽通过抑制生物膜形成和促进生物膜清除来快速杀死()，具有良好的血浆稳定性、极低的细胞毒性、最小的溶血活性，并且对凝血系统没有明显的促进作用。值得注意的是，RK22 的给药显著抑制了体内()感染和临床耐药株。因此，这些发现强调了 RK22 作为治疗()感染的理想候选药物的潜力。
