{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/27553"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/27553","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"The Potential Role of Cathelicidin Peptides for the Treatment of Lower Respiratory Tract Infections","abstract":"Bacterial pneumonia, one of the leading causes of hospitalization and mortality worldwide, is caused by the colonization of invasive bacteria in the airways, leading to pulmonary inflammation and lung dysfunction. The development of antibiotic resistant bacterial infections has limited the effectiveness of current therapeutics and is particularly concerning in the setting of chronic bacterial infections, such as observed in cystic fibrosis and ventilator-associated pneumonia. The development of novel therapeutics for the treatment of multi-drug resistant bacterial pneumonia is urgently needed. The overall objective of this body of work was the development of a new therapeutic compound to treat multi-drug resistant bacterial infections in the lung. It was hypothesized that a cathelicidin/exogenous surfactant compound could be developed as a novel therapeutic agent for the treatment of bacterial pneumonia. To test this hypothesis, we first screened several cathelicidin peptides combined with a commercial exogenous surfactant, bovine lipid extract surfactant (BLES), and identified a lead compound (CATH-2) for further testing. Following this, we investigated three main outcomes: 1) the antimicrobial activity of CATH-2 and BLES+CATH-2 against multi-drug resistant, clinically isolated bacteria; 2) the immunomodulatory potential of both CATH-2 and BLES+CATH-2 in vivo; and 3) the bactericidal activity of BLES+CATH-2 treatment in vivo, using two models of bacterial pneumonia. It was discovered that CATH-2 was able to kill bacteria in vitro. In addition, CATH-2 killed bacteria administered into the lungs of mice did not induce an inflammatory response in vivo, and that the ability to prevent this inflammation was maintained by BLES+CATH-2. Finally, while BLES+CATH-2 is able to kill multi-drug resistant, clinically derived bacteria in vitro, there is little bactericidal activity of BLES+CATH-2 in in vivo models of bacterial pneumonia. Overall, we identified the therapeutic potential of BLES+CATH-2 for use as a therapeutic treatment for bacterial pneumonia. Despite promising in vitro activity, we were unable to show bactericidal activity for BLES+CATH-2 in vivo. Future directions will require the optimization of the surfactant-cathelicidin compound in order to develop a viable therapeutic for clinical practice.","abstract_html":"Bacterial pneumonia, one of the leading causes of hospitalization and mortality worldwide, is caused by the colonization of invasive bacteria in the airways, leading to pulmonary inflammation and lung dysfunction. The development of antibiotic resistant bacterial infections has limited the effectiveness of current therapeutics and is particularly concerning in the setting of chronic bacterial infections, such as observed in cystic fibrosis and ventilator-associated pneumonia. The development of novel therapeutics for the treatment of multi-drug resistant bacterial pneumonia is urgently needed. The overall objective of this body of work was the development of a new therapeutic compound to treat multi-drug resistant bacterial infections in the lung. It was hypothesized that a cathelicidin/exogenous surfactant compound could be developed as a novel therapeutic agent for the treatment of bacterial pneumonia. To test this hypothesis, we first screened several cathelicidin peptides combined with a commercial exogenous surfactant, bovine lipid extract surfactant (BLES), and identified a lead compound (CATH-2) for further testing. Following this, we investigated three main outcomes: 1) the antimicrobial activity of CATH-2 and BLES+CATH-2 against multi-drug resistant, clinically isolated bacteria; 2) the immunomodulatory potential of both CATH-2 and BLES+CATH-2 in vivo; and 3) the bactericidal activity of BLES+CATH-2 treatment in vivo, using two models of bacterial pneumonia. It was discovered that CATH-2 was able to kill bacteria in vitro. In addition, CATH-2 killed bacteria administered into the lungs of mice did not induce an inflammatory response in vivo, and that the ability to prevent this inflammation was maintained by BLES+CATH-2. Finally, while BLES+CATH-2 is able to kill multi-drug resistant, clinically derived bacteria in vitro, there is little bactericidal activity of BLES+CATH-2 in in vivo models of bacterial pneumonia. Overall, we identified the therapeutic potential of BLES+CATH-2 for use as a therapeutic treatment for bacterial pneumonia. Despite promising in vitro activity, we were unable to show bactericidal activity for BLES+CATH-2 in vivo. Future directions will require the optimization of the surfactant-cathelicidin compound in order to develop a viable therapeutic for clinical practice.","abstract_has_math":false,"creators":["Banaschewski, Brandon John Harrison"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Physiology and Pharmacology","degree_department":null,"school":null,"contributors":[],"advisors":["Ruud Veldhuizen","Cory Yamashita"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-09-06","date_published":"2017-09-06","updated_at":"2026-07-27T21:55:56Z","subjects":["Cathelicidins","exogenous pulmonary surfactant","inflammation","cytokines","bacterial pneumonia","cystic fibrosis","ventilator-associated pneumonia","Pseudomonas aeruginosa"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/27553","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Ruud Veldhuizen","Cory Yamashita"]},{"key":"dc:creator","label":"Author","values":["Banaschewski, Brandon John Harrison"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T15:30:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T15:30:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2017-09-06"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology and Pharmacology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph D"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cathelicidins","exogenous pulmonary surfactant","inflammation","cytokines","bacterial pneumonia","cystic fibrosis","ventilator-associated pneumonia","Pseudomonas aeruginosa"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/27553"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Bacterial pneumonia, one of the leading causes of hospitalization and mortality worldwide, is caused by the colonization of invasive bacteria in the airways, leading to pulmonary inflammation and lung dysfunction. The development of antibiotic resistant bacterial infections has limited the effectiveness of current therapeutics and is particularly concerning in the setting of chronic bacterial infections, such as observed in cystic fibrosis and ventilator-associated pneumonia. The development of novel therapeutics for the treatment of multi-drug resistant bacterial pneumonia is urgently needed. The overall objective of this body of work was the development of a new therapeutic compound to treat multi-drug resistant bacterial infections in the lung. It was hypothesized that a cathelicidin/exogenous surfactant compound could be developed as a novel therapeutic agent for the treatment of bacterial pneumonia. To test this hypothesis, we first screened several cathelicidin peptides combined with a commercial exogenous surfactant, bovine lipid extract surfactant (BLES), and identified a lead compound (CATH-2) for further testing. Following this, we investigated three main outcomes: 1) the antimicrobial activity of CATH-2 and BLES+CATH-2 against multi-drug resistant, clinically isolated bacteria; 2) the immunomodulatory potential of both CATH-2 and BLES+CATH-2 in vivo; and 3) the bactericidal activity of BLES+CATH-2 treatment in vivo, using two models of bacterial pneumonia. It was discovered that CATH-2 was able to kill bacteria in vitro. In addition, CATH-2 killed bacteria administered into the lungs of mice did not induce an inflammatory response in vivo, and that the ability to prevent this inflammation was maintained by BLES+CATH-2. Finally, while BLES+CATH-2 is able to kill multi-drug resistant, clinically derived bacteria in vitro, there is little bactericidal activity of BLES+CATH-2 in in vivo models of bacterial pneumonia. Overall, we identified the therapeutic potential of BLES+CATH-2 for use as a therapeutic treatment for bacterial pneumonia. Despite promising in vitro activity, we were unable to show bactericidal activity for BLES+CATH-2 in vivo. Future directions will require the optimization of the surfactant-cathelicidin compound in order to develop a viable therapeutic for clinical practice."]},{"key":"dc:title","label":"Title","values":["The Potential Role of Cathelicidin Peptides for the Treatment of Lower Respiratory Tract Infections"]}]}],"canonical_facts":{"dc:contributor.advisor":["Ruud Veldhuizen","Cory Yamashita"],"dc:creator":["Banaschewski, Brandon John Harrison"],"dc:date.accessioned":["2025-07-10T15:30:38Z"],"dc:date.available":["2025-07-10T15:30:38Z"],"dc:date.issued":["2017-09-06"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Bacterial pneumonia, one of the leading causes of hospitalization and mortality worldwide, is caused by the colonization of invasive bacteria in the airways, leading to pulmonary inflammation and lung dysfunction. The development of antibiotic resistant bacterial infections has limited the effectiveness of current therapeutics and is particularly concerning in the setting of chronic bacterial infections, such as observed in cystic fibrosis and ventilator-associated pneumonia. The development of novel therapeutics for the treatment of multi-drug resistant bacterial pneumonia is urgently needed. The overall objective of this body of work was the development of a new therapeutic compound to treat multi-drug resistant bacterial infections in the lung. It was hypothesized that a cathelicidin/exogenous surfactant compound could be developed as a novel therapeutic agent for the treatment of bacterial pneumonia. To test this hypothesis, we first screened several cathelicidin peptides combined with a commercial exogenous surfactant, bovine lipid extract surfactant (BLES), and identified a lead compound (CATH-2) for further testing. Following this, we investigated three main outcomes: 1) the antimicrobial activity of CATH-2 and BLES+CATH-2 against multi-drug resistant, clinically isolated bacteria; 2) the immunomodulatory potential of both CATH-2 and BLES+CATH-2 in vivo; and 3) the bactericidal activity of BLES+CATH-2 treatment in vivo, using two models of bacterial pneumonia. It was discovered that CATH-2 was able to kill bacteria in vitro. In addition, CATH-2 killed bacteria administered into the lungs of mice did not induce an inflammatory response in vivo, and that the ability to prevent this inflammation was maintained by BLES+CATH-2. Finally, while BLES+CATH-2 is able to kill multi-drug resistant, clinically derived bacteria in vitro, there is little bactericidal activity of BLES+CATH-2 in in vivo models of bacterial pneumonia. Overall, we identified the therapeutic potential of BLES+CATH-2 for use as a therapeutic treatment for bacterial pneumonia. Despite promising in vitro activity, we were unable to show bactericidal activity for BLES+CATH-2 in vivo. Future directions will require the optimization of the surfactant-cathelicidin compound in order to develop a viable therapeutic for clinical practice."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/27553"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Cathelicidins","exogenous pulmonary surfactant","inflammation","cytokines","bacterial pneumonia","cystic fibrosis","ventilator-associated pneumonia","Pseudomonas aeruginosa"],"dc:title":["The Potential Role of Cathelicidin Peptides for the Treatment of Lower Respiratory Tract Infections"],"dc:type":["thesis"],"thesis:degree_discipline":["Physiology and Pharmacology"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:55:56Z"}