In vitro and in vivo evaluation of BMAP-derived peptides for the treatment of cystic fibrosis-related pulmonary infections.
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.
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127, Trieste, Italy.
Mario
M
Mardirossian
Department of Medical, Oral, and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.|Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Via L. Polacchi 11, 66100, Chieti, Italy.
Arianna
A
Pompilio
Department of Medical, Oral, and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.|Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Via L. Polacchi 11, 66100, Chieti, Italy.
Valentina
V
Crocetta
Department of Medical, Oral, and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.|Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Via L. Polacchi 11, 66100, Chieti, Italy.
Serena
S
De Nicola
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127, Trieste, Italy.
Filomena
F
Guida
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127, Trieste, Italy.
Margherita
M
Degasperi
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127, Trieste, Italy.
Renato
R
Gennaro
Department of Medical, Oral, and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.|Center of Excellence on Aging, "G. d'Annunzio" University Foundation, Via L. Polacchi 11, 66100, Chieti, Italy.
Giovanni
G
Di Bonaventura
Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, 34127, Trieste, Italy. mscocchi@units.it.
Marco
M
Scocchi
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D006801:Humans; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy*; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D013211:Staphylococcus aureus / Q000502:physiology*
D023181:Antimicrobial Cationic Peptides; C102359:BMAP-27; C102360:BMAP-28; D010455:Peptides; D011506:Proteins
Antimicrobial peptide; BMAP; Biofilm; Cathelicidin; Cystic fibrosis; In vivo degradation; Multidrug-resistance