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Pseudomonas aeruginosa-induced infection and degradation of human wound fluid and skin proteins ex vivo are eradicated by a synthetic cationic polymer

Werthen, M; Davoudi, Mina LU ; Sonesson, Andreas LU ; Nitsche, Patric LU ; Mörgelin, Matthias LU ; Blom, K and Schmidtchen, Artur LU (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)
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author
organization
publishing date
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
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
2007-11-05 13:50:19
date last changed
2017-12-10 03:38:45
@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},
  keyword      = {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},
  volume       = {54},
  year         = {2004},
}