Dermal Wound Transcriptomic Responses to Infection with Pseudomonas aeruginosa versus Klebsiella pneumoniae in a Rabbit Ear Wound Model.

摘要

Background: Bacterial infections of wounds impair healing and worsen scarring. We hypothesized that transcriptome analysis of wounds infected with Klebsiella pneumoniae (Kp.) or Pseudomonas aeruginosa (P.o.) would indicate host responses associated with the worse healing of P.o. than Kp. infected wounds. Methods: Wounds created on post operative day (POD) 0 were infected during the inflammatory phase of healing on POD3 and were harvested on POD4 for microarray and transcriptome analysis. Other wounds received topical antibiotic after infection for 24 hours to promote biofilm development, and were harvested on POD6 or POD12. Results: Wounds infected for 24 hours, relative to uninfected wounds, elevated transcripts of immune response functions characteristic of infiltrating leukocytes. But P.o. infected wounds elevated many more transcripts and to higher levels than Kp. infected wounds. Coincidently, suppressed transcripts of both wounds enriched into stress response pathways, including EIF2 signaling; however, this was more extensive for P.o. infected wounds, including many fold more transcripts enriching in the 'cell death' annotation, suggesting resident cutaneous cell toxicity in response to a more damaging P.a. inflammatory milieu. The POD6 wounds were colonized with biofilm but expressed magnitudes fewer immune response transcripts with no stress response enrichments. However, elevated transcripts of P.o. infected wounds were inferred to be regulated by type I interferons, similar to a network unique to P.o. infected wounds on POD4. On POD12, transcripts that were more elevated in Kp. infected wounds suggested healing, while transcripts more elevated in P.o. infected wounds indicated inflammation. Conclusions: An extensive inflammatory response of wounds was evident from upregulated transcripts 24 hours after infection with either bacterium, but the response was more intense for P.o. than K.p. infected wounds.