Background: Antibiotic-resistant is considered one of the critical health challenges in the management of infectious diseases. Resistant bacterial strains to different antibacterial agents have been spread worldwide. Anti-microbial peptides (AMPs), also called host defense peptides, have a broad spectrum of activity and targeting even to multi-drug resistant (MDR) bacteria, therefore, they have been extensively studied and developed as novel therapeutic antibacterial agents.
Objectives: The study aims to design a novel SK4 hybrid peptide with improved characteristics compared with the BMAP-27 and Cecropin-A natural parents' peptides.
Methods: The bioinformatic analysis of the SK4 peptide compared with the parents BMAP-27 and Cecropin-A peptides was conducted and fully characterized using specialized software. The antimicrobial and antibiofilm activity of SK4 was tested, followed by a synergistic study with five conventional antibiotics (Levofloxacin, Rifampicin, Chloramphenicol, Doxycycline, and Ampicillin). Finally, the cytotoxicity against horse erythrocytes and mammalian cells was assessed.
Results: The SK4 peptide demonstrated broad-spectrum antimicrobial activity against both grampositive and gram-negative bacteria. The peptide also did not show any hemolytic activity even when used at concentrations ten folds higher than its MICs value. The SK4 peptide also showed a synergistic mode of action when combined with antibiotics, which resulted in a significant decrease in MIC values for both the peptide and the antibiotics.
Conclusion: The SK4 peptide showed better activity, selectivity, and safety profile than the parent peptides, making it a novel potential treatment for MDR bacterial infections.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1566524023666221031144028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Catecholamine induces endothelial dysfunction via Angiotensin II and intermediate conductance calcium activated potassium channel.
Biomed Pharmacother
August 2024
Department of Cardiology, Angiology, Hemostaseology and Medical Intensive Care, Medical Faculty Mannheim, University Medical Centre Mannheim (UMM), Heidelberg University, Mannheim, Germany; Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
Endothelial dysfunction contributes to the pathogenesis of Takotsubo syndrome (TTS). However, the exact mechanism underlying endothelial dysfunction in the setting of TTS has not been completely clarified. This study aims to investigate the roles of angiotensin II (Ang II) and intermediate-conductance Ca-activated K (SK4) channels in catecholamine-induced endothelial dysfunction.
View Article and Find Full Text PDFInvestigating the Impact of Electrostatic Interactions on Calmodulin Binding and Ca-Dependent Activation of the Calcium-Gated Potassium SK4 Channel.
Int J Mol Sci
April 2024
Département de Pharmacologie et Physiologie, Faculté de Médecine, Centre de Recherche de l'Institut de Cardiologie de Montréal, Université de Montréal, Montréal, QC H1T 1C8, Canada.
Ca binding to the ubiquitous Ca sensing protein calmodulin (CaM) activates the intermediate conductance Ca-activated SK4 channel. Potential hydrophilic pockets for CaM binding have been identified at the intracellular HA and HB helices in the C-terminal of SK4 from the three published cryo-EM structures of SK4. Single charge reversal substitutions at either site, significantly weakened the pull-down of SK4 by CaM wild-type (CaM), and decreased the TRAM-34 sensitive outward K current densities in native HEK293T cells when compared with SK4 WT measured under the same conditions.
View Article and Find Full Text PDFIdentification of Riluzole derivatives as novel calmodulin inhibitors with neuroprotective activity by a joint synthesis, biosensor, and computational guided strategy.
Biomed Pharmacother
May 2024
Department of Organic and Inorganic Chemistry, University of the Basque Country UPV/EHU, Leioa 48940, Spain; Biofisika Institute, CSIC-UPV/EHU, Leioa 48940, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao 48011, Spain. Electronic address:
The development of new molecules for the treatment of calmodulin related cardiovascular or neurodegenerative diseases is an interesting goal. In this work, we introduce a novel strategy with four main steps: (1) chemical synthesis of target molecules, (2) Förster Resonance Energy Transfer (FRET) biosensor development and in vitro biological assay of new derivatives, (3) Cheminformatics models development and in vivo activity prediction, and (4) Docking studies. This strategy is illustrated with a case study.
View Article and Find Full Text PDFMolecular dynamics simulations of the calmodulin-induced α-helix in the SK2 calcium-gated potassium ion channel.
J Biol Chem
February 2023
Donostia International Physics Center, Donostia, Spain; Departamento de Física, Universidad del País Vasco, UPV/EHU, Leioa, Spain; Centro de Física de Materiales CFM, CSIC-UPV/EHU, Donostia, Spain.
The family of small-conductance Ca-activated potassium ion channels (SK channels) is composed of four members (SK1, SK2, SK3, and SK4) involved in neuron-firing regulation. The gating of these channels depends on the intracellular Ca concentration, and their sensitivity to this ion is provided by calmodulin (CaM). This protein binds to a specific region in SK channels known as the calmodulin-binding domain (CaMBD), an event which is essential for their gating.
View Article and Find Full Text PDFBlockade of SK4 channels suppresses atrial fibrillation by attenuating atrial fibrosis in canines with prolonged atrial pacing.
Int J Med Sci
December 2022
Department of Cardiology, Renmin Hospital of Wuhan University Wuhan City, Wuchang, Wuhan, China.
We previously found that intermediate conductance Ca-activated K channel (SK4) might be an important target in atrial fibrillation (AF). To investigate the role of SK4 in AF maintenance. Twenty beagles were randomly assigned to the sham group (n=6), pacing group (n=7), and pacing+TRAM-34 group (n=7).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!