Chemistry Institute, Faculty of Exact and Natural Sciences, University of Antioquia, A.A. 1226, Medellin, 050010, Colombia.
Grupo de Investigación e Innovación Biomédica, Facultad de Ciencias Exactas y Aplicadas, Instituto Tecnológico Metropolitano, A.A. 54959, Medellín, 050010, Colombia.
J Membr Biol. 2024 Apr;257(1-2):51-61. doi: 10.1007/s00232-024-00306-3. Epub 2024 Feb 5.
Escherichia coli is the most common microorganism causing nosocomial or community-acquired bacteremia, and extended-spectrum β-lactamase-producing Escherichia coli isolates are identified worldwide with increasing frequency. For this reason, it is necessary to evaluate potential new molecules like antimicrobial peptides. They are recognized for their biological potential which makes them promising candidates in the fight against infections. The goal of this research was to evaluate the potential of the synthetic peptide ΔM3 on several extended-spectrum β-lactamase producing E. coli isolates. The antimicrobial and cytotoxic activity of the peptide was spectrophotometrically determined. Additionally, the capacity of the peptide to interact with the bacterial membrane was monitored by fluorescence microscopy and infrared spectroscopy. The results demonstrated that the synthetic peptide is active against Escherichia coli isolates at concentrations similar to Meropenem. On the other hand, no cytotoxic effect was observed in HaCaT keratinocyte cells even at 10 times the minimal inhibitory concentration. Microscopy results showed a permeabilizing effect of the peptide on the bacteria. The infrared results showed that ΔM3 showed affinity for the lipids of the microorganism's membrane. The results suggest that the ∆M3 interacts with the negatively charged lipids from the E. coli by a disturbing effect on membrane. Finally, the secondary structure experiments of the peptide showed a random structure in solution that did not change during the interaction with the membranes.
大肠埃希菌是引起医院获得性或社区获得性菌血症最常见的微生物，产超广谱β-内酰胺酶的大肠埃希菌分离株在全球范围内的检出率越来越高。因此，有必要评估像抗菌肽这样的潜在新分子。它们的生物学潜力得到了认可，使它们成为抗感染的有前途的候选物。本研究的目的是评估合成肽 ΔM3 对几种产超广谱β-内酰胺酶的大肠埃希菌分离株的潜在作用。通过分光光度法测定了该肽的抗菌和细胞毒性活性。此外，通过荧光显微镜和红外光谱监测肽与细菌膜的相互作用能力。结果表明，该合成肽对大肠埃希菌分离株的活性与美罗培南相似。另一方面，即使在最小抑菌浓度的 10 倍时，也未观察到对 HaCaT 角质形成细胞的细胞毒性作用。显微镜结果显示该肽对细菌有渗透作用。红外结果表明，ΔM3 与微生物膜的脂质具有亲和力。结果表明，ΔM3 通过对膜的干扰作用与大肠埃希菌的带负电荷的脂质相互作用。最后，该肽的二级结构实验表明，在溶液中呈无规则结构，与膜相互作用时不会发生变化。
