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 P. aeruginosa. Mice were sacrificed on postoperative day 6 and abdominal tissues analyzed for clinical signs of wound infection. To determine if specific wound tissues components induce bacterial virulence, P. aeruginosa was exposed to skin, fascia, and muscle. Results Gross wound infection due to P. aeruginosa was observed to be significantly increased in injured tissues vs non-injured (80% vs 10%) tissues (n=20/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 fascia demonstrated activation of multiple genes responsible for the synthesis of the iron scavenging molecule pyochelin. Conclusion 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.

Modeling Acinetobacter baumannii wound infections

“…We provide evidence that the pathogenesis of A. baumannii wound infections is dependent on the degree of tissue trauma and the composition of the wound milieu. We have previously shown that the wound environment plays a significant contributory role in infectious pathogenesis using a Pseudomonas aeruginosa wound infection model in which rectus muscle injury providing contact with fascia was sufficient for P. aeruginosa to cause wound infection through activation of its iron scavenging systems (28). However, as our current work demonstrated, a more severe insult combining muscle injury with ischemia was required for A. baumannii wound infection in mice.…”

“…However, as our current work demonstrated, a more severe insult combining muscle injury with ischemia was required for A. baumannii wound infection in mice. This difference may reflect a higher capacity of P. aeruginosa to trigger its virulence in response to multiple host derived signals (28–34), and hence explain, in part, its reputation as a highly virulent pathogen. Without the local microenvironmental cues present in a wound complicated by injury and ischemia, A. baumannii may not be sufficiently activated to cause a clinical wound infection.…”

Successful treatment of a unique chronic multi-bacterial scalp infection with N-chlorotaurine, N-bromotaurine and bromamine T

“…Their adaptation capacity to grow in diverse ecological niches, their alteration of virulence factor expression and, thus, their pathogenic behaviour due to their interaction with host elements explain their capability to produce a diversity of opportunistic infections [31]. Many strains of this complex are described as host invaders, especially during impairment of immune defence, and they are adequately described as human pathogens in various serious infections including wounds [31,32]. S. lugdunensis, a coagulase-negative coccus, was also isolated from the tissue swabs.…”

Preparing the Bowel for Surgery: Learning from the Past and Planning for the Future

“…Yet how and why bacteria in some circumstances seem to “be cleared away” is largely unstudied and therefore remains unknown. Advances in molecular microbiology might explain such a response as the net result of a complex and iterative dialogue between pathogen and host whose final interplay ends in a type of “molecular détente (38). ”…”