Pseudomonas aeruginosa-induced infection and degradation of human wound fluid and skin proteins ex vivo are eradicated by a synthetic cationic polymer
(2004) In Journal of Antimicrobial Chemotherapy 54(4). p.772-779- Abstract
- Objectives: Antimicrobial peptides are important effectors of innate immunity. Bacteria display multiple defence mechanisms against these peptides. For example, Pseudomonas aeruginosa releases potent proteinases that inactivate the human cathelicidin LL-37. Hence, in conditions characterized by persistent bacterial colonization, such as in P. aeruginosa-infected skin wounds, there is a need for efficient means of reducing bacterial load. Here, the effect of the cationic molecule polyhexamethylenebiguanide (PHMB) was evaluated. Methods: Infection models in human wound fluid and human skin were established. Radial diffusion methods, bacterial growth and bactericidal assays were used for determination of effects of PHMB on bacteria in the... (More)
- Objectives: Antimicrobial peptides are important effectors of innate immunity. Bacteria display multiple defence mechanisms against these peptides. For example, Pseudomonas aeruginosa releases potent proteinases that inactivate the human cathelicidin LL-37. Hence, in conditions characterized by persistent bacterial colonization, such as in P. aeruginosa-infected skin wounds, there is a need for efficient means of reducing bacterial load. Here, the effect of the cationic molecule polyhexamethylenebiguanide (PHMB) was evaluated. Methods: Infection models in human wound fluid and human skin were established. Radial diffusion methods, bacterial growth and bactericidal assays were used for determination of effects of PHMB on bacteria in the presence of plasma, wound fluid or human skin. At the protein and tissue levels, SDS-PAGE, light microscopy and scanning electron microscopy were used to study the effects of P. aeruginosa infection before and after addition of PHMB. Results: PHMB killed common ulcer-derived bacteria in the presence of human wound fluid. Furthermore, elastase-expressing P. aeruginosa completely degraded wound fluid proteins as well as human skin during infection ex vivo. The infection, and consequent protein degradation, was reversed by PHMB. Conclusions: The ex vivo infection models presented here should be helpful in the screening of novel antimicrobials and constitute a prerequisite for future clinical studies. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/266379
- author
- Werthen, M ; Davoudi, Mina LU ; Sonesson, Andreas LU ; Nitsche, Patric LU ; Mörgelin, Matthias LU ; Blom, K and Schmidtchen, Artur LU
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- bacteria, wound healing, antimicrobials, proteolysis, polyhexamethylenebiguanide
- in
- Journal of Antimicrobial Chemotherapy
- volume
- 54
- issue
- 4
- pages
- 772 - 779
- publisher
- Oxford University Press
- external identifiers
-
- pmid:15355938
- wos:000224207100011
- scopus:6344244516
- pmid:15355938
- ISSN
- 1460-2091
- DOI
- 10.1093/jac/dkh407
- language
- English
- LU publication?
- yes
- id
- 7708c2fe-f7a8-4bcf-8da9-e41e5bcdaad3 (old id 266379)
- date added to LUP
- 2016-04-01 11:35:26
- date last changed
- 2022-04-20 18:57:28
@article{7708c2fe-f7a8-4bcf-8da9-e41e5bcdaad3, abstract = {{Objectives: Antimicrobial peptides are important effectors of innate immunity. Bacteria display multiple defence mechanisms against these peptides. For example, Pseudomonas aeruginosa releases potent proteinases that inactivate the human cathelicidin LL-37. Hence, in conditions characterized by persistent bacterial colonization, such as in P. aeruginosa-infected skin wounds, there is a need for efficient means of reducing bacterial load. Here, the effect of the cationic molecule polyhexamethylenebiguanide (PHMB) was evaluated. Methods: Infection models in human wound fluid and human skin were established. Radial diffusion methods, bacterial growth and bactericidal assays were used for determination of effects of PHMB on bacteria in the presence of plasma, wound fluid or human skin. At the protein and tissue levels, SDS-PAGE, light microscopy and scanning electron microscopy were used to study the effects of P. aeruginosa infection before and after addition of PHMB. Results: PHMB killed common ulcer-derived bacteria in the presence of human wound fluid. Furthermore, elastase-expressing P. aeruginosa completely degraded wound fluid proteins as well as human skin during infection ex vivo. The infection, and consequent protein degradation, was reversed by PHMB. Conclusions: The ex vivo infection models presented here should be helpful in the screening of novel antimicrobials and constitute a prerequisite for future clinical studies.}}, author = {{Werthen, M and Davoudi, Mina and Sonesson, Andreas and Nitsche, Patric and Mörgelin, Matthias and Blom, K and Schmidtchen, Artur}}, issn = {{1460-2091}}, keywords = {{bacteria; wound healing; antimicrobials; proteolysis; polyhexamethylenebiguanide}}, language = {{eng}}, number = {{4}}, pages = {{772--779}}, publisher = {{Oxford University Press}}, series = {{Journal of Antimicrobial Chemotherapy}}, title = {{Pseudomonas aeruginosa-induced infection and degradation of human wound fluid and skin proteins ex vivo are eradicated by a synthetic cationic polymer}}, url = {{http://dx.doi.org/10.1093/jac/dkh407}}, doi = {{10.1093/jac/dkh407}}, volume = {{54}}, year = {{2004}}, }