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Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing
The intricate biological process of cutaneous wound healing is achieved through precise and highly programmed events. Dermal fibroblasts and keratinocytes play a significant role in the process of reepithelialization during wound healing. Pathogenic bacteria such as Pseudomonas aeruginosa (P. aerugi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683349/ https://www.ncbi.nlm.nih.gov/pubmed/32801335 http://dx.doi.org/10.1038/s41374-020-00478-1 |
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author | Prasad, Alevoor Srinivas Bharath Shruptha, Padival Prabhu, Vijendra Srujan, Cheruku Nayak, Usha Yogendra Anuradha, Calicut Kini Rao Ramachandra, Lingadakai Keerthana, Prasad Joshi, Manjunath B. Murali, Thokur Sreepathy Satyamoorthy, Kapaettu |
author_facet | Prasad, Alevoor Srinivas Bharath Shruptha, Padival Prabhu, Vijendra Srujan, Cheruku Nayak, Usha Yogendra Anuradha, Calicut Kini Rao Ramachandra, Lingadakai Keerthana, Prasad Joshi, Manjunath B. Murali, Thokur Sreepathy Satyamoorthy, Kapaettu |
author_sort | Prasad, Alevoor Srinivas Bharath |
collection | PubMed |
description | The intricate biological process of cutaneous wound healing is achieved through precise and highly programmed events. Dermal fibroblasts and keratinocytes play a significant role in the process of reepithelialization during wound healing. Pathogenic bacteria such as Pseudomonas aeruginosa (P. aeruginosa) may delay the proliferative phase of wound repair by secreting their proteins leading to delayed or impaired wound healing. We have analyzed three virulent strains of P. aeruginosa isolated from the wound environment which also differed in their ability to produce biofilms. Mass spectrometric analysis of differentially expressed secreted proteins by three virulent strains of P. aeruginosa revealed peptides from pseudolysin and protease IV expressed from lasB and prpL genes. Pseudolysin and protease IV recombinant proteins were tested for their ability to modulate wound healing in several cell types of wound microenvironment in in vitro and in vivo models. Both pseudolysin and protease IV inhibited migration and survival of fibroblasts, keratinocytes, and endothelial cells. In three dimensional spheroid endothelial models and matrigel assays these proteins impeded sprouting and tube formation. In a mouse model of excision wound, pseudolysin and protease IV treatment showed reduced collagen content, inhibited neovascularization and epithelialization, and delayed wound contraction. Furthermore, pseudolysin and protease IV treatment resulted in a significant increase in plasma IL-6 levels when compared to vehicle control and control, suggesting the induction of a state of prolonged inflammation. Taken together, our data indicate pseudolysin and protease IV secreted from biofilm producing and antibiotic resistant P. aeruginosa in wound microenvironment produce both local and systemic effects that is detrimental to the maintenance of tissue homeostasis. Hence, these proteins may serve as potential therapeutic targets toward better clinical management of wounds. |
format | Online Article Text |
id | pubmed-7683349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-76833492020-12-03 Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing Prasad, Alevoor Srinivas Bharath Shruptha, Padival Prabhu, Vijendra Srujan, Cheruku Nayak, Usha Yogendra Anuradha, Calicut Kini Rao Ramachandra, Lingadakai Keerthana, Prasad Joshi, Manjunath B. Murali, Thokur Sreepathy Satyamoorthy, Kapaettu Lab Invest Article The intricate biological process of cutaneous wound healing is achieved through precise and highly programmed events. Dermal fibroblasts and keratinocytes play a significant role in the process of reepithelialization during wound healing. Pathogenic bacteria such as Pseudomonas aeruginosa (P. aeruginosa) may delay the proliferative phase of wound repair by secreting their proteins leading to delayed or impaired wound healing. We have analyzed three virulent strains of P. aeruginosa isolated from the wound environment which also differed in their ability to produce biofilms. Mass spectrometric analysis of differentially expressed secreted proteins by three virulent strains of P. aeruginosa revealed peptides from pseudolysin and protease IV expressed from lasB and prpL genes. Pseudolysin and protease IV recombinant proteins were tested for their ability to modulate wound healing in several cell types of wound microenvironment in in vitro and in vivo models. Both pseudolysin and protease IV inhibited migration and survival of fibroblasts, keratinocytes, and endothelial cells. In three dimensional spheroid endothelial models and matrigel assays these proteins impeded sprouting and tube formation. In a mouse model of excision wound, pseudolysin and protease IV treatment showed reduced collagen content, inhibited neovascularization and epithelialization, and delayed wound contraction. Furthermore, pseudolysin and protease IV treatment resulted in a significant increase in plasma IL-6 levels when compared to vehicle control and control, suggesting the induction of a state of prolonged inflammation. Taken together, our data indicate pseudolysin and protease IV secreted from biofilm producing and antibiotic resistant P. aeruginosa in wound microenvironment produce both local and systemic effects that is detrimental to the maintenance of tissue homeostasis. Hence, these proteins may serve as potential therapeutic targets toward better clinical management of wounds. Nature Publishing Group US 2020-08-15 2020 /pmc/articles/PMC7683349/ /pubmed/32801335 http://dx.doi.org/10.1038/s41374-020-00478-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Prasad, Alevoor Srinivas Bharath Shruptha, Padival Prabhu, Vijendra Srujan, Cheruku Nayak, Usha Yogendra Anuradha, Calicut Kini Rao Ramachandra, Lingadakai Keerthana, Prasad Joshi, Manjunath B. Murali, Thokur Sreepathy Satyamoorthy, Kapaettu Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title | Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title_full | Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title_fullStr | Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title_full_unstemmed | Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title_short | Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing |
title_sort | pseudomonas aeruginosa virulence proteins pseudolysin and protease iv impede cutaneous wound healing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683349/ https://www.ncbi.nlm.nih.gov/pubmed/32801335 http://dx.doi.org/10.1038/s41374-020-00478-1 |
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