Natural history of Acinetobacter baumannii infection in mice

PLoS One. 2019 Jul 18;14(7):e0219824. doi: 10.1371/journal.pone.0219824. eCollection 2019.


In 2017, the WHO identified Acinetobacter baumannii as the top priority for the development of new antibiotics. Despite the need for new antibiotics, there remains a lack of well validated preclinical tools for A. baumannii. Here, we characterize and validate a mouse model for A. baumannii translational research. Antibiotic sensitivity for meropenem, amikacin, and polymyxin b was determined by the broth microdilution MIC assay. LD100 inoculums, in both blood and lung infection models, were determined in male and female C3HeB/FeJ mice that were challenged with various A. baumannii clinical isolates. Blood (blood infection model) or blood and lung tissue (lung infection model) were collected from infected mice at 2 and 18 hours and the bacterial burden was determined by quantitative culture. Blood chemistry was analyzed using the iStat system. Cytokines (IL-1ß, TNF, IL-6, and IL-10) were measured in the blood and lung homogenate by ELISA assay. Lung sections (H&E stains) were scored by a pathologist. In the blood infection model, the cytokines and physiological data indicate that mice become moribund due to sepsis (low blood pH, falling bicarbonate, and a rising base deficit), whereas mice become moribund due to respiratory failure (low blood pH, rising bicarbonate, and a falling base deficit) in the oral aspiration pneumonia model. We also characterized the timing of changes in various clinical and biomarker endpoints, which can serve as a basis for future interventional studies. Susceptibility was generally similar across gender and infection route. However, we did observe that female mice were approximately 2-fold more sensitive to LAC-4 ColR in the blood infection model. We also observed that female mice were more than 10-fold more resistant to VA-AB41 in the oral aspiration pneumonia model. These results establish parameters to follow in order to assess efficacy of novel preventative and therapeutic approaches for these infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acinetobacter Infections / microbiology*
  • Acinetobacter Infections / pathology
  • Acinetobacter baumannii* / drug effects
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Biomarkers
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Mice
  • Microbial Sensitivity Tests


  • Anti-Bacterial Agents
  • Biomarkers