i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
INEB, Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135, Porto, Portugal.
Sci Rep. 2019 Jul 24;9(1):10753. doi: 10.1038/s41598-019-47108-5.
Urinary catheters are extensively used in hospitals, being responsible for about 75% of hospital-acquired infections. In this work, a de novo designed antimicrobial peptide (AMP) Chain201D was studied in the context of urinary catheter-associated infections. Chain201D showed excellent antimicrobial activity against relevant ATCC strains and clinical isolates of bacteria and yeast and demonstrated high stability in a wide range of temperatures, pH and salt concentrations. Moreover, the bactericidal activity of Chain201D immobilized on a model surface was studied against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), some of the most prevalent strains found in urinary catheter-associated infections. Chain201D was successfully tethered to ((1-mercapto-11-undecyl)-(tetra(ethylene glycol) (EG4)) terminated self-assembled monolayers (SAMs), (EG4-SAMs), activated by 1,1'-Carbonyldiimidazole (CDI) at different concentrations. Chain201D surfaces can bind and kill by contact a high percentage of adherent bacteria. These achievements are obtained without any peptide modification (for chemoselective conjugation) and without the use of a spacer. Moreover, increased amounts of immobilized AMP lead to higher numbers of adhered/dead bacteria, revealing a concentration-dependent behaviour and demonstrating that Chain201D has excellent potential for developing antimicrobial urinary catheters.
导尿管在医院中被广泛使用,其引发的医院获得性感染约占 75%。在这项工作中,研究了一种从头设计的抗菌肽(AMP)Chain201D 在与导尿管相关的感染中的作用。Chain201D 对相关 ATCC 菌株和临床分离的细菌和酵母表现出优异的抗菌活性,并且在广泛的温度、pH 值和盐浓度范围内具有高稳定性。此外,还研究了固定在模型表面上的 Chain201D 对大肠杆菌(E. coli)和金黄色葡萄球菌(S. aureus)的杀菌活性,这些是与导尿管相关的感染中最常见的菌株。Chain201D 成功地键合到(1-巯基-11-十一烷基)-(四(乙二醇)(EG4))终止的自组装单层(SAM)上,(EG4-SAMs)通过 1,1'-碳二亚胺(CDI)在不同浓度下激活。Chain201D 表面可以通过接触结合并杀死附着的大部分细菌。这些成就是在没有任何肽修饰(用于化学选择性偶联)和不使用间隔物的情况下获得的。此外,固定化 AMP 的量增加会导致更多的附着/死亡细菌,这表明存在浓度依赖性行为,并且证明 Chain201D 具有开发抗菌导尿管的巨大潜力。