An In Vivo Polymicrobial Biofilm Wound Infection Model to Study Interspecies Interactions

Trevor Dalton,Chase Watters,Kendra P Rumbaugh,John A Griswold,Scot E Dowd,Yan Sun,Randall D Wolcott,Jean Louis Herrmann

doi:10.1371/journal.pone.0027317

Abstract

Chronic wound infections are typically polymicrobial; however, most in vivo studies have focused on monospecies infections. This project was designed to develop an in vivo, polymicrobial, biofilm-related, infected wound model in order to study multispecies biofilm dynamics and in relation to wound chronicity. Multispecies biofilms consisting of both Gram negative and Gram positive strains, as well as aerobes and anaerobes, were grown in vitro and then transplanted onto the wounds of mice. These in vitro-to-in vivo multi-species biofilm transplants generated polymicrobial wound infections, which remained heterogeneous with four bacterial species throughout the experiment. We observed that wounded mice given multispecies biofilm infections displayed a wound healing impairment over mice infected with a single-species of bacteria. In addition, the bacteria in the polymicrobial wound infections displayed increased antimicrobial tolerance in comparison to those in single species infections. These data suggest that synergistic interactions between different bacterial species in wounds may contribute to healing delays and/or antibiotic tolerance.

Highlights

Infections of the dermis, including burns, surgical site infections and non-healing diabetic foot ulcers affect over a million people, cause thousands of deaths and cost billions of dollars in direct medical costs in the United States annually [1,2,3,4,5,6,7]
We choose four aerobic and anaerobic bacterial species most commonly detected in human wounds (Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and Finegoldia magna) [11] as our representative polymicrobial cohort
Due to the technical challenges of co-culturing different species of bacteria, there is a dearth of reports investigating polymicrobial infections in wounds [36]

Summary

Introduction

Infections of the dermis, including burns, surgical site infections and non-healing diabetic foot ulcers affect over a million people, cause thousands of deaths and cost billions of dollars in direct medical costs in the United States annually [1,2,3,4,5,6,7]. Several other groups of immunocompromised patient populations are plagued by slow-healing and non-healing wounds. These include trauma and burn victims, cancer patients and pressure ulcers in the elderly [1,2,3,4,5,6,7]

Objectives

Methods

Results

Conclusion