Pseudomonas Aeruginosa Theft Biofilm Require Host Lipids of Cutaneous Wound.

Abstract

OBJECTIVE:

This work addressing complexities in wound infection, seeks to test the reliance of bacterial pathogen Pseudomonas aeruginosa (PA) on host skin lipids to form biofilm with pathological consequences.

BACKGROUND:

PA biofilm causes wound chronicity. Both CDC as well as NIH recognizes biofilm infection as a threat leading to wound chronicity. Chronic wounds on lower extremities often lead to surgical limb amputation.

METHODS:

An established preclinical porcine chronic wound biofilm model, infected with PA or Pseudomonas aeruginosa ceramidase mutant (PA ∆Cer ), was used.

RESULTS:

We observed that bacteria drew resource from host lipids to induce PA ceramidase expression by three orders of magnitude. PA utilized product of host ceramide catabolism to augment transcription of PA ceramidase. Biofilm formation was more robust in PA compared to PA ∆Cer . Downstream products of such metabolism such as sphingosine and sphingosine-1-phosphate were both directly implicated in the induction of ceramidase and inhibition of peroxisome proliferator-activated receptor (PPAR)δ, respectively. PA biofilm, in a ceram-idastin-sensitive manner, also silenced PPARδ via induction of miR-106b. Low PPARδ limited ABCA12 expression resulting in disruption of skin lipid homeostasis. Barrier function of the wound-site was thus compromised.

CONCLUSIONS:

This work demonstrates that microbial pathogens must co-opt host skin lipids to unleash biofilm pathogenicity. Anti-biofilm strategies must not necessarily always target the microbe and targeting host lipids at risk of infection could be productive. This work may be viewed as a first step, laying fundamental mechanistic groundwork, toward a paradigm change in biofilm management.

• Authors: Mithun Sinha, Nandini Ghosh, Dayanjan S Wijesinghe, Shomita S Mathew-Steiner, Amitava Das, Kanhaiya Singh, Mohamed El Masry, Savita Khanna, Hiroyuki Inoue, Katsuhisa Yamazaki, Manabu Kawada, Gayle M Gordillo, Sashwati Roy, Chandan K Sen
• Journal: Annals of surgery (Ann Surg) Vol. 277 Issue 3 Pg. e634-e647 (03 01 2023) ISSN: 1528-1140 [Electronic] United States
• PMID: 35129518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Ceramidases
• PPAR delta

Topics

• Animals
• Ceramidases
• Lower Extremity
• PPAR delta
• Pseudomonas aeruginosa
• Swine