Development of acute Pseudomonas aeruginosa and Acinetobacter baumannii lung infection models in mice using oropharyngeal aspiration.

Bacterial infections caused by antimicrobial resistant pathogens such as Pseudomonas aeruginosa and Acinetobacter baumannii can cause potentially fatal infections in susceptible individuals, with respiratory tract infections among the most common presentation. There is a real need to develop novel treatments or prophylactic interventions to combat these infections. The development of any new treatment or vaccine requires robust, reliable animal models for their preclinical evaluation. In particular, the bacterial burden needs to be accurately determined before and after administration of the potential therapy under evaluation to quantitate the effectiveness of the treatment. We provide a reliable non-invasive murine model of acute lung infection with either P. aeruginosa or A. baumannii using an oropharyngeal aspiration technique. This non-surgical technique to deliver suspensions into mouse lungs is less stressful to animals than other techniques. It allowed uniform bilateral distribution of the bacterial dose resulting in even colonisation of both lungs. The optimal timepoint for humane killing and organ harvest was 24 h after challenge for both pathogens, and at least 4x106 and 107 CFU/mouse were needed to establish P. aeruginosa or A. baumannii infection, respectively. These optimised mouse pneumonia models offer a valuable tool for studying P. aeruginosa and A. baumannii infections and evaluating therapeutic interventions against them.