O48 – Muscle Injury and Ischemia Contribute to the Pathogenesis of A. baumannii Infection
Author(s):
Background: Acinetobacter baumannii wound infections are associated with high mortality in extensive military injuries involving deep extremity muscle trauma, but rarely cause wound infections in civilians.
Hypothesis: We hypothesized that A. baumannii wound infections are a result of bidirectional cross-signaling between injured/ischemic host tissues and bacteria that make them particularly prevalent in blast injuries of major muscle groups. The aim of this study was to develop a model of A. baumannii infection that would allow for the identification of such signals.
Methods: A muscle injury/ischemia model of A. baumannii infection was developed by exposing the rectus abdominus muscle via a skin incision and inoculating 100μL of 10^5 CFUs to the rectus muscle for 2-3 min, followed by a saline wash, then skin closure. Acinetobacter baumannii (AC) infection to the rectus muscle was created in groups of mice with and without muscle injury (light crush injury) and with and without muscle ischemia (suture ligation of muscle). On post-operative day 7 (POD7), wounds were examined for purulence, HIF1α, AC colony counts, and AC virulence expression using Galleria mellonella virulence assays.
Results: Gross infection (purulence) occurred in 100% of mice subjected to AC inoculation onto injured and ischemic muscle (n=30, p<0.01), which demonstrated a higher degree of HIF1α expression (see Figure). No infection/pus was noted in all other treatment groups, i.e. muscle injury alone, ischemia alone, no muscle injury, no ischemia. In treatment groups where AC was inoculated onto both ischemic and injured muscle, there was a higher bacterial count (10-fold) compared to all other groups. In this group we also noted that AC shifted its colony morphotype to a rough-edge colony appearance compared to the normal smooth edged colonies observed in all other groups. Rough colony morphotypes were more lethal to Galleria mellonella than smooth colonies (n=15 p<0.05).
Conclusions: Muscle injury and ischemia may play a role in enhancing the virulence of A. baumannii and may explain its lethal effect in traumatic extremity injury. The role of HIF in this process remains to be elucidated.