Back to Search
Start Over
Effective antimicrobial activity of Cbf-14, derived from a cathelin-like domain, against penicillin-resistant bacteria.
- Source :
-
Biomaterials . May2016, Vol. 87, p32-45. 14p. - Publication Year :
- 2016
-
Abstract
- 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-K 16 . 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01429612
- Volume :
- 87
- Database :
- Academic Search Index
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 113539524
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2016.02.011