A polyalanine peptide derived from polar fish with anti-infectious activities
Marlon H. Cardoso, Suzana M. Ribeiro, Diego O. Nolasco, César de la Fuente-Núñez, Mário R. Felício, Sónia Gonçalves, Carolina O. Matos, Luciano M. Liao, Nuno C. Santos, Robert E. W. Hancock, Octávio L. Franco, Ludovico Migliolo
Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fishPleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silicotools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.
Circular dichroism, Secondary structure, Vesicle interactions, Pharmaceutical, Biochemistry