Bioluminescent Murine Models of Bacterial Sepsis and Scald Wound Infections for Antimicrobial Efficacy Testing

PLoS One. 2018 Jul 16;13(7):e0200195. doi: 10.1371/journal.pone.0200195. eCollection 2018.

Abstract

There are very few articles in the literature describing continuous models of bacterial infections that mimic disease pathogenesis in humans and animals without using separate cohorts of animals at each stage of disease. In this work, we developed bioluminescent mouse models of partial-thickness scald wound infection and sepsis that mimic disease pathogenesis in humans and animals using a recombinant luciferase-expressing Staphylococcus aureus strain (Xen29). Two days post-scald wound infection, mice were treated twice daily with a 2% topical mupirocin ointment for 7 days. For sepsis experiments, mice were treated intraperitoneally with 6 mg/kg daptomycin 2 h and 6 h post-infection and time to moribund monitored for 72 h. Consistent bacterial burden data were obtained from individual mice by regular photon intensity quantification on a Xenogen IVIS Lumina XRMS Series III biophotonic imaging system, with concomitant significant reduction in photon intensities in drug-treated mice. Post-mortem histopathological examination of wounds and bacterial counts in blood correlated closely with disease severity and total flux obtained from Xen29. The bioluminescent murine models provide a refinement to existing techniques of multiple bacterial enumeration during disease pathogenesis and promote animal usage reduction. The models also provide an efficient and information-rich platform for preclinical efficacy evaluation of new drug classes for treating acute and chronic human and animal bacterial infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteremia / diagnostic imaging
  • Bacteremia / drug therapy*
  • Bacteremia / pathology
  • Burns / diagnostic imaging
  • Burns / drug therapy
  • Burns / pathology
  • Disease Models, Animal*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Mice
  • Microbial Sensitivity Tests* / methods
  • Mupirocin / pharmacology
  • Staphylococcal Infections / diagnostic imaging
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / genetics*
  • Wound Infection / diagnostic imaging
  • Wound Infection / drug therapy*
  • Wound Infection / pathology

Substances

  • Anti-Bacterial Agents
  • Luminescent Proteins
  • Mupirocin

Grant support

This study was funded by Australian Research Council (ARC; arc.gov.au) Linkage Project LP130100736 to SWP and DJT, with Luoda Pharma as the Partner Organization, and by an ARC Linkage grant (LP110200770) to SWP and DJT, with Neoculi Pty Ltd as the Partner Organization. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Partner Organizations (Luoda Pharma and Neoculi Pty Ltd) provided support in the form of salary for SWP but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of SWP are articulated in the 'author contributions' section.