Identification and Characterization of RK22, a Novel Antimicrobial Peptide from Hirudinaria manillensis against Methicillin Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus potentially a...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-09, Vol.24 (17), p.13453
Main Authors: Lu, Xiaoyu, Yang, Min, Zhou, Shengwen, Yang, Shuo, Chen, Xiran, Khalid, Mehwish, Wang, Kexin, Fang, Yaqun, Wang, Chaoming, Lai, Ren, Duan, Zilei
Format: Article
Language:English
Subjects:
Alzheimer's disease
Antibiotics
Anticoagulants
Antimicrobial agents
antimicrobial peptide
Biofilms
Cytotoxicity
Defense mechanisms
Drug dosages
Drug resistance
E coli
Exocrine glands
Hirudinaria manillensis
Peptides
Plasma
RK22
Staphylococcus aureus
Staphylococcus infections
Viral infections
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Summary:Staphylococcus aureus (S. aureus) infections are a leading cause of morbidity and mortality, which are compounded by drug resistance. By manipulating the coagulation system, S. aureus gains a significant advantage over host defense mechanisms, with hypercoagulation induced by S. aureus 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 S. aureus 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 Hirudinaria manillensis (H. manillensis) through bioinformatic analysis, and then synthesized it, which exhibited good antimicrobial activity against S. aureus, including a clinically resistant strain with a minimal inhibitory concentration (MIC) of 6.25 μg/mL. The RK22 peptide rapidly killed S. aureus 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 S. aureus infection and the clinically resistant strain in vivo. Thus, these findings highlight the potential of RK22 as an ideal treatment candidate against S. aureus infection.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241713453