Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing

Alevoor, Srinivas Bharath Prasad and Padival, Shruptha and Cheruku, Srujan and Nayak, Usha Yogendra and Rao, Anuradha CK and Lingadakai, Ramachandra and Keerthana, Prasad and Joshi, Manjunath B and Thokur, Sreepathy Murali and Kapaettu, Satyamoorthy (2020) Pseudomonas aeruginosa virulence proteins pseudolysin and protease IV impede cutaneous wound healing. Laboratory Investigation, 100. pp. 1532-1550. ISSN 0023-6837

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Abstract

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 in�ammation. 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

Item Type: Article
Subjects: Information Sciences > MCIS Manipal
Life Sciences > MLSC Manipal
Medicine > KMC Manipal > Pathology
Pharmacy > MCOPS Manipal > Pharmaceutics
Medicine > KMC Manipal > Surgery
Depositing User: KMC Library
Date Deposited: 12 Mar 2021 07:02
Last Modified: 12 Mar 2021 07:02
URI: http://eprints.manipal.edu/id/eprint/156465

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