Enzymatic synthesis of poly(catechin)-antibiotic conjugates: an antimicrobial approach for indwelling catheters

abstract

Biofilm formation in urinary indwelling catheters is one of the most critical issues that patients face. Catheters were coated with poly(catechin)-antibiotic conjugates with enhanced antimicrobial properties. Catechin was conjugated with two antibiotics, namely trimethoprim (TMP) and sulfamethoxazole (SMZ) via activation with N,N'-disuccinimidyl carbonate (DSC) and subsequent coupling to molecules containing alpha-amine moieties. Silicone and polyurethane catheters were functionalized in situ through laccase oxidation of catechin-antibiotic conjugates. Four antimicrobial coatings were produced, namely with poly(catechin), poly(catechin)-TMP, poly(catechin)-SMZ and poly(catechin)-TMP-SMZ. The bacterial adhesion reduction was tested on the functionalized devices using gram-negative and gram-positive strains. The most significant reduction in adhesion was observed with poly(catechin)-TMP (gram-negative -85 % and gram-positive -87 %) and with poly(catechin)-TMP-SMZ (gram-negative -85 % and gram-positive -91 %). The cytotoxicity to mammalian cells was tested by indirect contact for 5 days and revealed that all the tested coatings supported more than 90 % of viable cells. A promising approach for the increase of the indwelling catheter lifespan was developed aiming to reduce catheter-associated chronic infections.

keywords

BACTERIAL OUTER-MEMBRANE; STAPHYLOCOCCUS-AUREUS; ANTIBACTERIAL PROPERTIES; BIOFILM RESISTANCE; TRIMETHOPRIM; ANTIBIOTICS; POLYPHENOLS; FLAVONOIDS; COMBINATION; MECHANISMS

subject category

Biotechnology & Applied Microbiology

authors

Goncalves, I; Abreu, AS; Matama, T; Ribeiro, A; Gomes, AC; Silva, C; Cavaco-Paulo, A

our authors

acknowledgements

The authors would like to acknowledge Pronefro (Portugal) and Degania (Israel) for supplying polyurethane and silicone catheters, respectively. The author Idalina Goncalves would like to acknowledge the NOVO project (FP7-HEALTH-2011.2.3.1-5) for funding. This work was partly supported by FEDER through POFC-COMPETE and by Portuguese funds from Fundacao para a Ciencia e a Tecnologia (FCT) through the project PEst-OE/BIA/UI4050/2014. The authors Carla Silva and Teresa Matama would like to acknowledge FCT for their scholarships SFRH/BPD/46515/2008 and SFRH/BPD/47555/2008.

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