| Autor: |
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 |
| Zdroj: |
Laboratory Investigation; December 2020, Vol. 100 Issue: 12 p1532-1550, 19p |
| Abstrakt: |
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. aeruginosaisolated 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. aeruginosarevealed peptides from pseudolysin and protease IV expressed from lasBand prpLgenes. 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. aeruginosain 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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink