Cuero-Amu Kelin, Daniela Bonilla-Velásquez Laura, Vargas-Casanova Yerly, Lucía Leal-Castro Aura, Marcela Parra-Giraldo Claudia, Giselle López-Sánchez Amalia, Fierro-Medina Ricardo, García-Castañeda Javier, Rivera-Monroy Zuly
Instituto de Biotecnología, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 45 No 26-85, 11321, Bogotá, Colombia.
Pontificia Universidad Javeriana, Carrera 7 No. 43-82, Bogotá, Colombia.
Chem Biodivers. 2025 Mar;22(3):e202401734. doi: 10.1002/cbdv.202401734. Epub 2024 Nov 22.
Peptides containing the sequences RRWQWR and RRWQWRMKKLG 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)-K-Ahx-C) exhibited significant antibacterial activity against sensitive, resistant, and multidrug-resistant clinical isolates of E. coli. Peptide 3: RRWQWR-Nal-KKLG; MIC=16 μM, [F]: (RRWQWRFKKLG)-K-Ahx; MIC=15 μM, 17: (RRWQWRFK)-K-Ahx; MIC=9 μM, and LfcinB (20-25): (RRWQWR)-K-Ahx; MIC=11 μM 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 [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.
合成了源自牛乳铁蛋白(LfcinB)的含有RRWQWR和RRWQWRMKKLG序列的肽,并评估了它们对大肠杆菌参考菌株以及敏感和耐药临床分离株的抗菌效果。四分支多抗原肽(MAP)((RRWQWR)-K-Ahx-C) 对大肠杆菌的敏感、耐药和多重耐药临床分离株均表现出显著的抗菌活性。肽3:RRWQWR-Nal-KKLG;最低抑菌浓度(MIC)=16 μM,[F]:(RRWQWRFKKLG)-K-Ahx;MIC=15 μM,17:(RRWQWRFK)-K-Ahx;MIC=9 μM,以及LfcinB (20-25):(RRWQWR)-K-Ahx;MIC=11 μM对大肠杆菌菌株表现出最高的抗菌活性,在MIC时具有杀菌作用且溶血作用小于5%,治疗指数>1。观察到肽[F]和17与环丙沙星(CIP)或头孢曲松(CEF)具有协同作用。用亚致死浓度的CIP对大肠杆菌ATCC 25922进行长时间处理会诱导该菌株产生耐药性,而一些肽不会诱导耐药性。这些肽可被认为是治疗由耐药大肠杆菌菌株引起的感染的有前途的候选药物。