Abstract
Background: Pseudomonas aeruginosa forms antibiotic-resistant biofilms that are responsible for the treatment failure or relapses of the bacterial infections in the lungs of patients with cystic fibrosis (CF). The alginate lyases that target extracellular polysaccharide alginate of P. aeruginosa biofilms are promising therapeutic candidates for treatment of P. aeruginosa biofilm infections. Methods: Immunofluorescent staining and thin layer chromatography were used to demonstrate the alginolytic activity of the alginate lyase enzyme (AlyP1400) purified from a marine Pseudoalteromonas bacterium. Anti-biofilm activities of AlyP1400 were tested alone or in combination with antibiotics on the biofilms of a mucoid Pseudomonas aeruginosa clinical isolate CF27 that were cultivated in 96-well plates and a flow cell. Results: We showed that AlyP1400 facilitated antibiotic activities to eliminate CF27 biofilms. The combination of AlyP1400 with antibiotics reduced the biofilm biomass and boosted bactericidal activity of antibiotics. Importantly, we demonstrated that the enzymatic activity of AlyP1400 was required for its biofilm disruption activity and its synergy with antibiotics to eradicate biofilm cells. Conclusion: This work shed new light on the potential mechanisms of the therapeutic activity for the combinational use of alginate lyase and antibiotics to treat P. aeruginosa infections in CF lungs or other P. aeruginosa biofilm-related infections.
| Original language | English |
|---|---|
| Pages (from-to) | 264-270 |
| Number of pages | 7 |
| Journal | Journal of Cystic Fibrosis |
| Volume | 20 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2021 |
Bibliographical note
Funding Information:We would like to thank Stephen Whitefield at the Cellular & Molecular Digital Imaging (CMDI) core facility for the assistance in confocal microscopy experiments. The CMDI core facility is maintained as part of the Centralized Operation of Research Equipment and Support program of Dalhousie's Faculty of Medicine. We appreciate the anti-Pseudomonas aeruginosa alginate antibody MAb F429 as a generous gift from Dr. Gerald Pier from the Brigham and Women's Hospital, Harvard Medical School. This project is supported by the Cystic Fibrosis Canada Marsha Morton Early Career Investigator award . This project was also supported by a Nova Scotia Health Research Foundation Establishment Grant and a Canadian Institutes of Health Research Project Grant ( PJT165970 ) to Z.C.
Funding Information:
We would like to thank Stephen Whitefield at the Cellular & Molecular Digital Imaging (CMDI) core facility for the assistance in confocal microscopy experiments. The CMDI core facility is maintained as part of the Centralized Operation of Research Equipment and Support program of Dalhousie's Faculty of Medicine. We appreciate the anti-Pseudomonas aeruginosa alginate antibody MAb F429 as a generous gift from Dr. Gerald Pier from the Brigham and Women's Hospital, Harvard Medical School. This project is supported by the Cystic Fibrosis Canada Marsha Morton Early Career Investigator award. This project was also supported by a Nova Scotia Health Research Foundation Establishment Grant and a Canadian Institutes of Health Research Project Grant (PJT165970) to Z.C.
Publisher Copyright:
© 2020
ASJC Scopus Subject Areas
- Pediatrics, Perinatology, and Child Health
- Pulmonary and Respiratory Medicine
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
