title: Validation of a novel murine wound model of Acinetobacter baumannii infection.
abstract: Patients recovering from traumatic injuries or surgery often require weeks to months of hospitalization, increasing the risk for wound and surgical site infections caused by ESKAPE pathogens, which include A. baumannii (the ESKAPE pathogens are Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). As new therapies are being developed to counter A. baumannii infections, animal models are also needed to evaluate potential treatments. Here, we present an excisional, murine wound model in which a diminutive inoculum of a clinically relevant, multidrug-resistant A. baumannii isolate can proliferate, form biofilms, and be effectively treated with antibiotics. The model requires a temporary, cyclophosphamide-induced neutropenia to establish an infection that can persist. A 6-mm-diameter, full-thickness wound was created in the skin overlying the thoracic spine, and after the wound bed was inoculated, it was covered with a dressing for 7 days. Uninoculated control wounds healed within 13 days, whereas infected, placebo-treated wounds remained unclosed beyond 21 days. Treated and untreated wounds were assessed with multiple quantitative and qualitative techniques that included gross pathology, weight loss and recovery, wound closure, bacterial burden, 16S rRNA community profiling, histopathology, peptide nucleic acid-fluorescence in situ hybridization, and scanning electron microscopy assessment of biofilms. The range of differences that we are able to identify with these measures in antibiotic- versus placebo-treated animals provides a clear window within which novel antimicrobial therapies can be assessed. The model can be used to evaluate antimicrobials for their ability to reduce specific pathogen loads in wounded tissues and clear biofilms. Ultimately, the mouse model approach allows for highly powered studies and serves as an initial multifaceted in vivo assessment prior to testing in larger animals.
authors.affiliation: Department of Wound Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Thompson
authors.forename: Chad C
authors.initials: CC
authors.lastname: Black
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pavlicek
authors.forename: Cary L
authors.initials: CL
authors.lastname: Honnold
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Wise
authors.forename: Yonas A
authors.initials: YA
authors.lastname: Alamneh
authors.forename: Jay K
authors.initials: JK
authors.lastname: Moon
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kessler
authors.forename: Yuanzheng
authors.initials: Y
authors.lastname: Si
authors.forename: Robert
authors.initials: R
authors.lastname: Williams
authors.forename: Suleyman
authors.initials: S
authors.lastname: Yildirim
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Kirkup
authors.forename: Romanza K
authors.initials: RK
authors.lastname: Green
authors.forename: Eric R
authors.initials: ER
authors.lastname: Hall
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Palys
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Zurawski
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii; D000818:Animals; D018441:Biofilms; D004195:Disease Models, Animal; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D014946:Wound Infection / Q000382:microbiology*