{"id":{"repo_id":"minho-thes","oai_identifier":"oai:repositorium.uminho.pt:1822/89029"},"canonical_url":"https://search.dev.ndltd.org/etd/minho-thes/oai:repositorium.uminho.pt:1822/89029","repository":{"repo_id":"minho-thes","name":"Universidade do Minho","base_url":"http://repositorium.sdum.uminho.pt/oai/request"},"display":{"title":"Functionalization of PVC using a mussel-inspired coating strategy to target the polymicrobial nature of ventilator-associated pneumonia","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Graínha, Tânia Raquel Rodrigues"],"institution":"Universidade do Minho","degree_name":"Doutoramento em Engenharia Química e Biológica","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Pereira, Maria Olívia","Alves, Diana Filipa Barros"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023-12-11","date_published":"2023-12-11","updated_at":"2026-08-21T16:46:36Z","subjects":["Antimicrobial coatings","Endotracheal tube","Polymicrobial biofilms","Ventilator-associated pneumonia","Pneumonia associada à ventilação mecânica","Tubo endotraqueal","Biofilmes polimicrobianos","Revestimentos antimicrobianos"],"languages":["eng"],"rights":["openAccess"],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/1822/89029","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"source_record":{"url":"http://repositorium.sdum.uminho.pt/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arepositorium.uminho.pt%3A1822%2F89029","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Pereira, Maria Olívia","Alves, Diana Filipa Barros"]},{"key":"dc:creator","label":"Author","values":["Graínha, Tânia Raquel Rodrigues"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2024-02-23T14:59:13Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2024-12-11T07:00:14Z"]},{"key":"dc:date.issued","label":"Date","values":["2023-12-11"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F136544%2F2018/PT","info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBTM-SAL%2F29841%2F2017/PT","info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04469%2F2013/PT","info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04469%2F2019/PT"]},{"key":"dc:type","label":"Dc Type","values":["doctoralThesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doutoramento em Engenharia Química e Biológica"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Universidade do Minho"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Antimicrobial coatings","Endotracheal tube","Polymicrobial biofilms","Ventilator-associated pneumonia","Pneumonia associada à ventilação mecânica","Tubo endotraqueal","Biofilmes polimicrobianos","Revestimentos antimicrobianos"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["openAccess"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1822/89029"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.","A pneumonia associada à ventilação mecânica (PAV) é uma infeção nosocomial comum e apresenta elevadas taxas de mortalidade e morbilidade associadas. A presença do tubo endotraqueal (TET) é um fator de risco para o desenvolvimento da PAV pois é propenso à adesão microbiana e formação de biofilme; por isso, são necessárias estratégias para conferir propriedades antimicrobianas aos TETs. Como tal, este projeto de doutoramento teve como objetivo desenvolver um revestimento antimicrobiano para aplicar no TET e prevenir a ocorrência da PAV. Uma vez que a natureza polimicrobiana (intra- e inter-reino) da PAV é de particular interesse, este trabalho também teve como objetivo contribuir para uma melhor compreensão das interações dentro destes consórcios bem como avaliar o seu impacto nos resultados antimicrobianos das superfícies desenvolvidas. Usando uma abordagem in silico, os dados experimentais sobre a base molecular das interações P. aeruginosa - C. albicans, dois agentes patogénicos importantes relacionados com a PAV, foram sistematicamente curados e depositados online. Os dados curados reconstruídos como redes revelaram entidades-chave que regulam estas interações, potenciais alvos terapêuticos e possíveis inibidores, o que ajudou na seleção dos compostos antimicrobianos para os estudos in vitro. Paralelamente, foi feita a funcionalização de policloreto de vinilo (PVC) usando uma estratégia de adesão baseada na dopamina, utilizando critérios de segurança, para prevenir a adesão única, dupla e tripla e a formação de biofilmes de agentes patogénicos importantes relacionados com a VAP: P. aeruginosa, Staphylococcus aureus e C. albicans. A estratégia foi aplicada com sucesso na imobilização de 9 compostos (naturais e sintéticos) em PVC. Os revestimentos que continham CIP apresentaram boa atividade inibitória contra biofilmes de espécies únicas de P. aeruginosa e S. aureus, enquanto que aqueles que continham AmB foram capazes de prevenir biofilmes de C. albicans. A co-imobilização destes agentes conferiu ao PVC atividade antimicrobiana de amplo espectro capaz de prevenir a formação de biofilmes de espécies únicas, duplas e triplas até 48 h, apresentando também características biocompatíveis. Para tempos mais longos, os revestimentos mostraram eficácia inferior após 72 h contra S. aureus e após 5 dias contra P. aeruginosa e S. aureus, mas ainda demonstraram atividade inibitória contra C. albicans. Por outro lado, a aplicação de uma única dose de CIP às 48 h aumentou o efeito antimicrobiano do PVC funcionalizado, garantindo a sua atividade de inibição tripla até 5 dias. Desta forma, esta estratégia de revestimento possui grande potencial para ser explorada no desenvolvimento de TET para combater a PAV."]},{"key":"dc:title","label":"Title","values":["Functionalization of PVC using a mussel-inspired coating strategy to target the polymicrobial nature of ventilator-associated pneumonia"]}]}],"canonical_facts":{"dc:contributor.advisor":["Pereira, Maria Olívia","Alves, Diana Filipa Barros"],"dc:creator":["Graínha, Tânia Raquel Rodrigues"],"dc:date.accessioned":["2024-02-23T14:59:13Z"],"dc:date.available":["2024-12-11T07:00:14Z"],"dc:date.issued":["2023-12-11"],"dc:description.abstract":["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.","A pneumonia associada à ventilação mecânica (PAV) é uma infeção nosocomial comum e apresenta elevadas taxas de mortalidade e morbilidade associadas. A presença do tubo endotraqueal (TET) é um fator de risco para o desenvolvimento da PAV pois é propenso à adesão microbiana e formação de biofilme; por isso, são necessárias estratégias para conferir propriedades antimicrobianas aos TETs. Como tal, este projeto de doutoramento teve como objetivo desenvolver um revestimento antimicrobiano para aplicar no TET e prevenir a ocorrência da PAV. Uma vez que a natureza polimicrobiana (intra- e inter-reino) da PAV é de particular interesse, este trabalho também teve como objetivo contribuir para uma melhor compreensão das interações dentro destes consórcios bem como avaliar o seu impacto nos resultados antimicrobianos das superfícies desenvolvidas. Usando uma abordagem in silico, os dados experimentais sobre a base molecular das interações P. aeruginosa - C. albicans, dois agentes patogénicos importantes relacionados com a PAV, foram sistematicamente curados e depositados online. Os dados curados reconstruídos como redes revelaram entidades-chave que regulam estas interações, potenciais alvos terapêuticos e possíveis inibidores, o que ajudou na seleção dos compostos antimicrobianos para os estudos in vitro. Paralelamente, foi feita a funcionalização de policloreto de vinilo (PVC) usando uma estratégia de adesão baseada na dopamina, utilizando critérios de segurança, para prevenir a adesão única, dupla e tripla e a formação de biofilmes de agentes patogénicos importantes relacionados com a VAP: P. aeruginosa, Staphylococcus aureus e C. albicans. A estratégia foi aplicada com sucesso na imobilização de 9 compostos (naturais e sintéticos) em PVC. Os revestimentos que continham CIP apresentaram boa atividade inibitória contra biofilmes de espécies únicas de P. aeruginosa e S. aureus, enquanto que aqueles que continham AmB foram capazes de prevenir biofilmes de C. albicans. A co-imobilização destes agentes conferiu ao PVC atividade antimicrobiana de amplo espectro capaz de prevenir a formação de biofilmes de espécies únicas, duplas e triplas até 48 h, apresentando também características biocompatíveis. Para tempos mais longos, os revestimentos mostraram eficácia inferior após 72 h contra S. aureus e após 5 dias contra P. aeruginosa e S. aureus, mas ainda demonstraram atividade inibitória contra C. albicans. Por outro lado, a aplicação de uma única dose de CIP às 48 h aumentou o efeito antimicrobiano do PVC funcionalizado, garantindo a sua atividade de inibição tripla até 5 dias. Desta forma, esta estratégia de revestimento possui grande potencial para ser explorada no desenvolvimento de TET para combater a PAV."],"dc:identifier.uri":["https://hdl.handle.net/1822/89029"],"dc:language.iso":["eng"],"dc:relation":["info:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F136544%2F2018/PT","info:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBTM-SAL%2F29841%2F2017/PT","info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04469%2F2013/PT","info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04469%2F2019/PT"],"dc:rights":["openAccess"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"dc:subject":["Antimicrobial coatings","Endotracheal tube","Polymicrobial biofilms","Ventilator-associated pneumonia","Pneumonia associada à ventilação mecânica","Tubo endotraqueal","Biofilmes polimicrobianos","Revestimentos antimicrobianos"],"dc:title":["Functionalization of PVC using a mussel-inspired coating strategy to target the polymicrobial nature of ventilator-associated pneumonia"],"dc:type":["doctoralThesis"],"thesis:degree_name":["Doutoramento em Engenharia Química e Biológica"],"thesis:institution_name":["Universidade do Minho"]},"updated_at":"2026-08-21T16:46:36Z"}