Publicação
Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies
| Resumo: | Hospital-acquired infections caused by adaptive resistance mechanisms and enhanced virulence in pathogens, often within the challenging context of biofilms, have led to the development of alternative treatments. Bacteriophages, viruses that infect bacteria, have emerged as a potential alternative or complement to antibiotics, especially in complex cases involving multi-species biofilms. This thesis examined the combined effect of phages and antibiotics, investigating how it contributes to biofilm eradication while mitigating antibiotic resistance. It is crucial to note that phage-antibiotic combinations can sometimes hinder treatment, emphasizing the importance of understanding optimal timing, dosage, and combinations for maximizing therapeutic potential. Phage therapy shows promise due to its bacteriaspecific targeting and ability to penetrate biofilm layers. However, understanding how biofilm formation conditions influences the treatment out-come is very important for an effective standardization of in vitro phage/biofilm interaction studies. The initial study was focused on the effect of hydrodynamic conditions of biofilm formation on phage killing activity. Results revealed variations in structure of P. aeruginosa biofilm formed under dynamic and static conditions, and a better phage performance against biofilms formed in dynamic conditions. These results demonstrate the need to develop and adopt standard conditions to assay phage/biofilm interactions. Furthermore, the study evaluated the antibiofilm ability of a newly isolated P. aeruginosa phage (EPA1) and seven antibiotics against mono and dual-species biofilms. Simultaneous phage-antibiotic application significantly enhanced biofilm reduction, compared to individual treatments, while sequential application (first phage, then antibiotic) led to impressive biofilm eradication. Antibiotics concentration and the timing were pivotal factors influencing the effectiveness of combined treatment. To validate these findings, further experiments were conducted using a threedimensional lung epithelial model and an artificial wound model. Sequential phages and gentamicin treatment eradicated P. aeruginosa biofilms in the lung model. Similarly, phage EPA1 and SAFA with GEN in sequential and multiple dose administrations effectively reduced biofilms of both P. aeruginosa and S. aureus. Simultaneous multiple dose administration showed the most promising results against the dualspecies biofilms. In conclusion, phage and antibiotic combination holds promise in controlling infectious biofilms. However, a careful consideration of optimal application strategies, including timing, dosage, and order of administration, is necessary to maximize the efficacy. Future research efforts should focus on elucidating these complex interactions to develop optimized therapeutic strategies against biofilmassociated infections, ultimately improving patient outcomes. |
|---|---|
| Autores principais: | Akturk, Ergun |
| Assunto: | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| Ano: | 2024 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade do Minho |
| Idioma: | inglês |
| Origem: | RepositóriUM - Universidade do Minho |
| _version_ | 1866270991735324672 |
|---|---|
| author | Akturk, Ergun |
| author_facet | Akturk, Ergun |
| author_role | author |
| contributor_name_str_mv | Azeredo, Joana Melo, Luís Daniel Rodrigues Universidade do Minho |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Akturk, Ergun\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Azeredo, Joana Melo, Luís Daniel Rodrigues Universidade do Minho |
| datacite.creators.creator.creatorName.fl_str_mv | Akturk, Ergun |
| datacite.date.Accepted.fl_str_mv | 2024-04-15T00:00:00Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| datacite.titles.title.fl_str_mv | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| dc.contributor.none.fl_str_mv | Azeredo, Joana Melo, Luís Daniel Rodrigues Universidade do Minho |
| dc.creator.none.fl_str_mv | Akturk, Ergun |
| dc.date.Accepted.fl_str_mv | 2024-04-15T00:00:00Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/1822/92446 |
| dc.language.none.fl_str_mv | eng |
| dc.rights.cclincense.fl_str_mv | http://creativecommons.org/licenses/by-nc-sa/4.0/ |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.rights.rights.copyright.fl_str_mv | openAccess |
| dc.subject.none.fl_str_mv | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| dc.title.fl_str_mv | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_db06 |
| description | Hospital-acquired infections caused by adaptive resistance mechanisms and enhanced virulence in pathogens, often within the challenging context of biofilms, have led to the development of alternative treatments. Bacteriophages, viruses that infect bacteria, have emerged as a potential alternative or complement to antibiotics, especially in complex cases involving multi-species biofilms. This thesis examined the combined effect of phages and antibiotics, investigating how it contributes to biofilm eradication while mitigating antibiotic resistance. It is crucial to note that phage-antibiotic combinations can sometimes hinder treatment, emphasizing the importance of understanding optimal timing, dosage, and combinations for maximizing therapeutic potential. Phage therapy shows promise due to its bacteriaspecific targeting and ability to penetrate biofilm layers. However, understanding how biofilm formation conditions influences the treatment out-come is very important for an effective standardization of in vitro phage/biofilm interaction studies. The initial study was focused on the effect of hydrodynamic conditions of biofilm formation on phage killing activity. Results revealed variations in structure of P. aeruginosa biofilm formed under dynamic and static conditions, and a better phage performance against biofilms formed in dynamic conditions. These results demonstrate the need to develop and adopt standard conditions to assay phage/biofilm interactions. Furthermore, the study evaluated the antibiofilm ability of a newly isolated P. aeruginosa phage (EPA1) and seven antibiotics against mono and dual-species biofilms. Simultaneous phage-antibiotic application significantly enhanced biofilm reduction, compared to individual treatments, while sequential application (first phage, then antibiotic) led to impressive biofilm eradication. Antibiotics concentration and the timing were pivotal factors influencing the effectiveness of combined treatment. To validate these findings, further experiments were conducted using a threedimensional lung epithelial model and an artificial wound model. Sequential phages and gentamicin treatment eradicated P. aeruginosa biofilms in the lung model. Similarly, phage EPA1 and SAFA with GEN in sequential and multiple dose administrations effectively reduced biofilms of both P. aeruginosa and S. aureus. Simultaneous multiple dose administration showed the most promising results against the dualspecies biofilms. In conclusion, phage and antibiotic combination holds promise in controlling infectious biofilms. However, a careful consideration of optimal application strategies, including timing, dosage, and order of administration, is necessary to maximize the efficacy. Future research efforts should focus on elucidating these complex interactions to develop optimized therapeutic strategies against biofilmassociated infections, ultimately improving patient outcomes. |
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| person_str_mv | Akturk, Ergun |
| publishDate | 2024 |
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| spelling | engporHospital-acquired infections caused by adaptive resistance mechanisms and enhanced virulence in pathogens, often within the challenging context of biofilms, have led to the development of alternative treatments. Bacteriophages, viruses that infect bacteria, have emerged as a potential alternative or complement to antibiotics, especially in complex cases involving multi-species biofilms. This thesis examined the combined effect of phages and antibiotics, investigating how it contributes to biofilm eradication while mitigating antibiotic resistance. It is crucial to note that phage-antibiotic combinations can sometimes hinder treatment, emphasizing the importance of understanding optimal timing, dosage, and combinations for maximizing therapeutic potential. Phage therapy shows promise due to its bacteriaspecific targeting and ability to penetrate biofilm layers. However, understanding how biofilm formation conditions influences the treatment out-come is very important for an effective standardization of in vitro phage/biofilm interaction studies. The initial study was focused on the effect of hydrodynamic conditions of biofilm formation on phage killing activity. Results revealed variations in structure of P. aeruginosa biofilm formed under dynamic and static conditions, and a better phage performance against biofilms formed in dynamic conditions. These results demonstrate the need to develop and adopt standard conditions to assay phage/biofilm interactions. Furthermore, the study evaluated the antibiofilm ability of a newly isolated P. aeruginosa phage (EPA1) and seven antibiotics against mono and dual-species biofilms. Simultaneous phage-antibiotic application significantly enhanced biofilm reduction, compared to individual treatments, while sequential application (first phage, then antibiotic) led to impressive biofilm eradication. Antibiotics concentration and the timing were pivotal factors influencing the effectiveness of combined treatment. To validate these findings, further experiments were conducted using a threedimensional lung epithelial model and an artificial wound model. Sequential phages and gentamicin treatment eradicated P. aeruginosa biofilms in the lung model. Similarly, phage EPA1 and SAFA with GEN in sequential and multiple dose administrations effectively reduced biofilms of both P. aeruginosa and S. aureus. Simultaneous multiple dose administration showed the most promising results against the dualspecies biofilms. In conclusion, phage and antibiotic combination holds promise in controlling infectious biofilms. However, a careful consideration of optimal application strategies, including timing, dosage, and order of administration, is necessary to maximize the efficacy. Future research efforts should focus on elucidating these complex interactions to develop optimized therapeutic strategies against biofilmassociated infections, ultimately improving patient outcomes.application/pdfporUnderstanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategiesAkturk, ErgunAzeredo, JoanaMelo, Luís Daniel RodriguesHostingInstitutionOrganizationalUniversidade do Minhoe-mailmailto:repositorium@usdb.uminho.ptrepositorium@usdb.uminho.ptURNurn:tid:1016179252024-04-1520242024-04-15T00:00:00ZHandlehttps://hdl.handle.net/1822/92446http://purl.org/coar/access_right/c_abf2open accessAntibioticBacteriophageBiofilmPhage-antibiotic combinationsAntibióticoBacteriófagoBiofilmeCombinações fago-antibióticos9534725 bytesliteraturehttp://purl.org/coar/resource_type/c_db06doctoral thesis2024-04-15http://creativecommons.org/licenses/by-nc-sa/4.0/openAccesshttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorium.uminho.pt/bitstreams/bb2ed516-a2d9-49d1-a754-308cc06724dd/download |
| spellingShingle | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies Akturk, Ergun Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| status | SINGLETON |
| subject.fl_str_mv | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| title | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| title_full | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| title_fullStr | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| title_full_unstemmed | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| title_short | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| title_sort | Understanding and controlling Pseudomonas aeruginosa and Staphylococcus aureus biofilms using combined phage-based strategies |
| topic | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| topic_facet | Antibiotic Bacteriophage Biofilm Phage-antibiotic combinations Antibiótico Bacteriófago Biofilme Combinações fago-antibióticos |
| url | https://hdl.handle.net/1822/92446 |
| visible | 1 |