Abstract
Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.
Highlights
Cm-p5 is an antimicrobial peptide composed of 12 amino acid residues (SRSELIVHQRLF-NH2, PDB ID: 2MP9, BMRB access number: 19973) with an α-helical structure
For more comprehensive antimicrobial examinations, the three Cm-p5 peptides were chemically resynthesized in large scale amounts (>100 mg batches) and were properly folded and analyzed, as described previously [3]
The rational design of AMPs using natural occurring AMPs as a template is an alternative strategy with promising results. This approach overcomes various limitations of natural AMPs including reduced systemic toxicity and enhanced activity in blood/serum [23]. Considering these advantages, we evaluated the antimicrobial action of three derivatives of the antifungal peptide Cm-p5 against multiresistant and problematic bacterial strains and some further major human pathogens
Summary
We used the following bacterial species: Streptococcus agalactiae ATCC 12403, Staphylococcus aureus MRSA ATCC 43300, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL) ATCC 700603, Acinetobacter baumanii ATCC19606, and Enterococcus faecium (VRE). Bacteria were cultured at 37 ◦ C/5% CO2 in liquid THY broth Oxoid, Hampshire, UK) supplemented with 0.5% yeast extract (BD, Miami, FA, USA). Pseudomonas aeruginosa PA14 (DSM 19882) was cultivated in liquid Müller–Hinton–Broth (Carl Roth, Karlsruhe, Germany) at 37 ◦ C, under orbital shaking at 160 rpm. 7H9-medium containing 7H9 BBL Middlebrook broth (BD), glycerol (Honeywell, Charlotte, NC, USA) OADC (Oelic Albumin Dextrose Catalase; BD), Tween 80 (Roth, Karlsruhe, Germany), and ddH2 O. The pH was adjusted between 7.2–7.4 and sterile filtration was performed with a 0.2-μm filter membrane (Thermo ScientificTM NalgeneTM Rapid-FlowTM , Thermo Scientific, Bremen, Germany)
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