title: Pseudomonas aeruginosa wound infection involves activation of its iron acquisition system in response to fascial contact.
abstract: BACKGROUND
  Wound infections are traditionally thought to occur when microbial burden exceeds the innate clearance capacity of host immune system. Here, we introduce the idea that the wound environment itself plays a significant contributory role to wound infection.
  
  
  METHODS
  We developed a clinically relevant murine model of soft tissue infection to explore the role of activation of microbial virulence in response to tissue factors as a mechanism by which pathogenic bacteria cause wound infections. Mice underwent abdominal skin incision and light muscle injury with a crushing forceps versus skin incision alone followed by topical inoculation of Pseudomonas aeruginosa. Mice were sacrificed on postoperative Day 6, and abdominal tissues were analyzed for clinical signs of wound infection. To determine if specific wound tissue components induce bacterial virulence, P. aeruginosa was exposed to the skin, fascia, and muscle.
  
  
  RESULTS
  Gross wound infection caused by P. aeruginosa was observed to be significantly increased in injured tissues versus noninjured (80% vs.10%) tissues (n = 20 per group, p < 0.0001). Exposure of P. aeruginosa to individual tissue components demonstrated that fascia significantly induced bacterial virulence as judged by the production of pyocyanin, a redox-active phenazine compound known to kill immune cells. Whole-genome transcriptional profiling of P. aeruginosa exposed to the fascia demonstrated activation of multiple genes responsible for the synthesis of the iron scavenging molecule pyochelin.
  
  
  CONCLUSIONS
  We conclude that wound elements, in particular fascia, may play a significant role in enhancing the virulence of P. aeruginosa and may contribute to the pathogenesis of clinical wound infection.
authors: From the Departments of Surgery (M.K., S.C., I.F., O.Z., J.C.A.), Radiology and Cellular Oncology (N.N.K.), and Medicine (Y.H., E.C.), University of Chicago, Chicago, Illinois. O.Z. and J.C.A. are senior coauthors.
authors: Moses
authors: M
authors: Kim
authors: Scott
authors: S
authors: Christley
authors: Nikolai N
authors: NN
authors: Khodarev
authors: Irma
authors: I
authors: Fleming
authors: Yong
authors: Y
authors: Huang
authors: Eugene
authors: E
authors: Chang
authors: Olga
authors: O
authors: Zaborina
authors: John C
authors: JC
authors: Alverdy
mesh_terms: D000009:Abdominal Muscles / Q000382:microbiology / Q000601:surgery; D000818:Animals; D004195:Disease Models, Animal; D005205:Fascia / Q000382:microbiology*; D020869:Gene Expression Profiling; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010636:Phenols / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity*; D013530:Surgical Wound Infection / Q000382:microbiology*; D013844:Thiazoles / Q000378:metabolism*; D014774:Virulence / Q000502:physiology*
chemical_list: D010636:Phenols; D013844:Thiazoles; C025316:pyochelin