Inhibition of Pseudomonas aeruginosa biofilm formation and expression of virulence genes by selective epimerization in the peptide Esculentin‐1a(1‐21)NH2

• DOI: 10.1111/febs.14940
• Publication Date: 2019-05-30T07:25:08Z
• Authors: Bruno Casciaro; Qiao Lin; Sergii Afonin; Maria Rosa Loffredo; Valeria de Turris; Volker Middel; Anne S. Ulrich; YuanPu Peter Di; Maria Luisa Mangoni
• Keywords: Pyoverdine

Pseudomonas aeruginosa is a pathogenic bacterium known to cause serious human infections, especially in immune‐compromised patients. This due its unique ability transform from drug‐tolerant planktonic more dangerous and treatment‐resistant sessile life form, called biofilm. Recently, two derivatives of the frog skin antimicrobial peptide esculentin‐1a, i.e. Esc(1‐21) D‐amino acids containing diastereomer Esc(1‐21)‐1c, were characterized for their powerful anti‐ Pseudomonal activity against both forms. Prevention biofilm formation already early stages could be even advantageous counteracting infections induced by this bacterium. In work, we studied how Esc(1‐21)‐1c can inhibit comparison parent clinically‐used conventional antibiotics, colistin aztreonam, when applied at dosages below minimal growth inhibitory concentration. Biofilm prevention was correlated peptides’ motility reduce production virulent metabolites, example, pyoverdine rhamnolipids. Furthermore, molecular mechanism underlying these activities evaluated studying effect on expression key genes involved virulence bacteria, as well monitoring binding bacterial signaling nucleotide ppGpp. Our results demonstrate that presence only sufficient downregulate ppGpp‐mediated biofilm‐associated genes, presumably result higher stability therefore prolonged interaction with nucleotide. Overall, studies should assist efficient design optimization new anti‐infective agents multiple pharmacologically beneficial properties.