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| Content Provider | Springer Nature Link |
|---|---|
| Author | Mardirossian, Mario Pompilio, Arianna Crocetta, Valentina Nicola, Serena Guida, Filomena Degasperi, Margherita Gennaro, Renato Di Bonaventura, Giovanni Scocchi, Marco |
| Copyright Year | 2016 |
| Abstract | Patients with cystic fibrosis require pharmacological treatment against chronic lung infections. The alpha-helical antimicrobial peptides BMAP-27 and BMAP-28 have shown to be highly active in vitro against planktonic and sessile forms of multidrug-resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Stenotrophomonas maltophilia cystic fibrosis strains. To develop small antibacterial peptides for therapeutic use, we tested shortened/modified BMAP fragments, and selected the one with the highest in vitro antibacterial activity and lowest in vivo acute pulmonary toxicity. All the new peptides have shown to roughly maintain their antibacterial activity in vitro. The 1–18 N-terminal fragment of BMAP-27, showing MIC90 of 16 µg/ml against P. aeruginosa isolates and strain-dependent anti-biofilm effects, showed the lowest pulmonary toxicity in mice. However, when tested in a murine model of acute lung infection by P. aeruginosa, BMAP-27(1–18) did not show any curative effect. If exposed to murine broncho-alveolar lavage fluid BMAP-27(1–18) was degraded within 10 min, suggesting it is not stable in pulmonary environment, probably due to murine proteases. Our results indicate that shortened BMAP peptides could represent a starting point for antibacterial drugs, but they also indicate that they need a further optimization for effective in vivo use. |
| Starting Page | 2253 |
| Ending Page | 2260 |
| Page Count | 8 |
| File Format | |
| ISSN | 09394451 |
| Journal | Amino Acids |
| Volume Number | 48 |
| Issue Number | 9 |
| e-ISSN | 14382199 |
| Language | English |
| Publisher | Springer Vienna |
| Publisher Date | 2016-06-06 |
| Publisher Place | Vienna |
| Access Restriction | Subscribed |
| Subject Keyword | Antimicrobial peptide Cathelicidin BMAP Cystic fibrosis Biofilm Multidrug-resistance In vivo degradation Biochemistry Analytical Chemistry Biochemical Engineering Life Sciences Proteomics Neurobiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Organic Chemistry Biochemistry Clinical Biochemistry |
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