Linear and Polyvalent Peptides with Potent Antimicrobial Activity Against Sensitive and Multidrug-Resistant E. c oli Clinical Isolates

Peptides containing the sequences (20)RRWQWR(25) and (20)RRWQWRMKKLG(30) derived from Bovine lactoferricin (LfcinB) were synthesized and their antibacterial effect against reference strains and sensitive and resistant clinical isolates of E. coli was evaluated. Tetra-branched multiple antigen peptide (MAP) ((RRWQWR)(2)-K-Ahx-C)(2) exhibited significant antibacterial activity against sensitive, resistant, and multidrug-resistant clinical isolates of E. coli. Peptide 3: RRWQWR-Nal-KKLG; MIC=16 mu M, (26)[F]: (RRWQWRFKKLG)(2)-K-Ahx; MIC=15 mu M, 17: (RRWQWRFK)(2)-K-Ahx; MIC=9 mu M, and LfcinB (20-25)(2): (RRWQWR)(2)-K-Ahx; MIC=11 mu M exhibited the highest antibacterial activity against E. coli strains, with bactericidal effect and haemolytic effect at MIC less than 5 % and a therapeutic index >1. A synergistic effect of peptides (26)[F] and 17 with ciprofloxacin (CIP) or ceftriaxone (CEF) was observed. Prolonged treatment of E. coli ATCC 25922 with sublethal concentrations of CIP induced resistance in this strain, whereas some peptides did not induce resistance. These peptides can be considered to be promising candidates for treating infections caused by resistant strains of E. coli.