title: Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model.
abstract: Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group (p < 0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p < 0.006). In addition, a higher concentration of interleukin-1beta in the chronic wounds of BALB/c mice was observed at day 7 (p < 0.02), despite a similar number of bacteria in the two mouse strains. The present study succeeded in establishing a chronic PA biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms. In conclusion, our findings indicate that improved infection control of chronic wounds reduces the inflammatory response and may improve healing.
authors: Department of Clinical Microbiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Hannah
authors: H
authors: Trøstrup
authors: Kim
authors: K
authors: Thomsen
authors: Lars J
authors: LJ
authors: Christophersen
authors: Hans P
authors: HP
authors: Hougen
authors: Thomas
authors: T
authors: Bjarnsholt
authors: Peter Ø
authors: PØ
authors: Jensen
authors: Nikolai
authors: N
authors: Kirkby
authors: Henrik
authors: H
authors: Calum
authors: Niels
authors: N
authors: Høiby
authors: Claus
authors: C
authors: Moser
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002056:Burns / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012867:Skin / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing; D014946:Wound Infection / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000464:Alginates; D000890:Anti-Infective Agents; D053583:Interleukin-1beta