Abstract
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.
Highlights
Bacterial resistance is becoming a significant threat to public health, and it is estimated that a failure to address this problem would result in 10 million deaths every year globally by 20501,2
One of the peptides that resulted from En-AP1 fragmentation, Met[11], had a moderate antimicrobial activity and was chosen as a template for rationally designing of a de novo AMP, which was synthesized from unnatural D-amino acids (D-AA)
Modifications were done to improve antimicrobial activity according to various parameters, such as positive charge, aliphatic index, and instability index[32,33]
Summary
E. coli has been the most prevalent strain found in urinary catheter-associated infections[11] This microorganism has long been resistant to TEM-1 β-lactamase and, more recently, has become resistant to extended-spectrum β-lactamases (ESBLs), carbapenemases or acquired plasmid-mediated quinolone resistance (PMQR)[11]. Considering this scenario, it is urgent to find alternatives to conventional antibiotics that can prevent/treat infections associated with urinary catheters. It has been previously shown that under certain conditions AMPs can maintain their antimicrobial activity when immobilized to different substrates[12,13,14,25] This strategy provides a higher AMP surface availability and a more homogeneous distribution over the surface than peptide incorporation or adsorption methods, where peptide aggregation or uneven distribution usually occurs[26]. Peptide covalent immobilization has been pointed out as a solution to overcome enzymatic degradation, increasing long-term stability and avoiding toxicity associated with the application of high AMP concentrations[27,28]
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