Effective antimicrobial activity of Cbf-14, derived from a cathelin-like domain, against penicillin-resistant bacteria

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• 作者：Lingman Ma ; Yanrong Wang ; Mengxiao Wang ; Yuwei Tian ; Wei Kang ; Hanhan Liu ; Hui Wang ; Jie Dou ; ^{doujie@cpu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Changlin Zhou ; ^{cl_zhou@cpu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Cbf-14 ; Antimicrobial activity ; Penicillin-resistant bacteria ; NDM-1-carrying bacteria ; Membrane permeation ; DNA binding
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：87
• 期：Complete
• 页码：32-45
• 全文大小：4089 K

文摘

Cbf-14, a cationic peptide derived from a cathelin-like domain, was designed by inserting the highly α-helical sequence RLLR into an antibacterial sequence and deleting the inactive amino acids in Cbf-K₁₆. Clinical penicillin-resistant isolates as well as NDM-1-carrying Escherichia coli and a correspondingly infected mice model were employed to evaluate Cbf-14 antibacterial activity. The results showed that Cbf-14 possessed potent antimicrobial effects with an MIC of 8–64 μg/ml, and killed almost all bacteria within 240 min. Cbf-14-treated mice achieved an 80% survival rate and approximate 2.5 log unit reduction in CFU in tissues; additionally, this peptide significantly suppressed the production of pro-inflammatory cytokines by the disaggregation of lipopolysaccharide (LPS), suggesting its anti-inflammatory effects. Furthermore, Cbf-14, concentration higher than 2 × MIC value, increased membrane uptake to NPN and PI dye by 96.2% and 63.7%, respectively, neutralised the negative zeta potential of LPS and bacteria surface, and induced 100% leakage of liposome-entrapped calcein and cytoplasmic membrane disruption of E. coli, indicating obvious membrane permeation. Finally, it bound to DNA and respectively evoked 85.0% and 63.3% inhibition of gene replication and protein expression of NDM-1 at sub-MIC concentration in E. coli BL21 (DE3)-NDM-1. These data indicated that Cbf-14 possessed effective antimicrobial activity against penicillin-resistant bacteria in vitro/vivo through membrane disruption, DNA binding, down-regulating NDM-1 expression by plasmid replication inhibition, and anti-inflammatory activity by LPS disaggregation, suggesting a potential anti-infective clinical agent.