Functionalization of PVC using a mussel-inspired coating strategy to target the polymicrobial nature of ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is a common nosocomial infection with high mortality and morbidity rates. The endotracheal tube (ETT) is a risk factor for developing VAP as they are prone to microbial adhesion and biofilm formation; hence, strategies to impart these devices with antimicrobial properties are in great need. As such, this PhD project aimed to engineer an antimicrobial coating for ETTs to prevent VAP occurrence. Since the polymicrobial (intra- and interkingdom) nature of VAP is of particular concern, this work also aimed to understand the interactions within these consortia as well as to inspect their impact on the efficacy of the engineered surfaces. Through an in silico approach, experimental data on the molecular basis of P. aeruginosa – C. albicans interactions, two VAP-relevant pathogens, were systematically curated and deposited in the new Inter- Species CrossTalk Database (www.ceb.uminho.pt/ISCTD). Data reconstructed as networks revealed key entities regulating these interactions, potential therapeutic targets, and possible inhibitors, which helped in antimicrobial compound selection for the in vitro tasks. In parallel, polyvinyl chloride (PVC) was functionalized using an adhesive dopamine-based strategy, applying safe-by-design criteria, to prevent single, dual, and triple adhesion and biofilm formation of VAPrelevant pathogens: P. aeruginosa, Staphylococcus aureus, and C. albicans. The coating strategy was successful in immobilizing nine compounds (natural and synthetic) on PVC. Coatings containing ciprofloxacin (CIP) inhibited P. aeruginosa and S. aureus while those containing amphotericin B (AmB) prevented C. albicans single-species biofilms. Co-immobilization of these agents imparted PVC with broadspectrum activity, impairing the formation of single, dual, and triple-species biofilms up to 48 h, while also displaying biocompatibility. Longer application times showed reduced efficacy after 72 h against S. aureus and after 5 days against P. aeruginosa and S. aureus, but still demonstrated activity against C. albicans. Bacteria recovered from the surfaces after 5 days revealed enhanced CIP tolerance, probably due to CIP exposure and, in the case of S. aureus, such traits could be attributed to its interaction with P. aeruginosa. Still, the application of a single CIP dose at 48 h boosted triple consortia inhibition for up to 5 days. As such, this coating strategy holds great potential to be further explored in ETT design to fight VAP.

Name thesis:degree_name

Doutoramento em Engenharia Química e Biológica

Grantor

Universidade do Minho

Year dc:date.issued

2023

Author dc:creator

• Graínha, Tânia Raquel Rodrigues

Advisors dc:contributor.advisor

• Pereira, Maria Olívia
• Alves, Diana Filipa Barros

• Antimicrobial coatings
• Endotracheal tube
• Polymicrobial biofilms
• Ventilator-associated pneumonia
• Pneumonia associada à ventilação mecânica
• Tubo endotraqueal
• Biofilmes polimicrobianos
• Revestimentos antimicrobianos

Statement dc:rights

• openAccess

Licence dc:rights.uri

• http://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1822/89029

OAI record oai:identifier

http://repositorium.sdum.uminho.pt/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arepositorium.uminho.pt%3A1822%2F89029