The BALB/c Mouse Model for the Evaluation of Therapies to Treat Infections with Aerosolized Burkholderia pseudomallei

Abstract

Burkholderia pseudomallei, the causative agent of the disease melioidosis, has been isolated from the environment in 45 countries. The treatment of melioidosis is complex, requiring lengthy antibiotic regimens, which can result in the relapse of the disease following treatment cessation. It is important that novel therapies to treat infections with B. pseudomallei be assessed in appropriate animal models, and discussions regarding the different protocols used between laboratories are critical. A ‘deep dive’ was held in October 2020 focusing on the use of the BALB/c mouse model and the inhalational route of infection to evaluate new antibiotic therapies.

Detection of low-level animal-to-animal transmission in BALB/c mouse models of melioidosis

“…This low-level of transmission should be considered when analyzing data obtained from lengthy therapeutic studies using more sensitive animal models (i.e. BALB/c mouse or hamster) (Amemiya et al, 2017;Nelson et al, 2023). Whilst it is impractical to singly house mice for numerous reasons (including ethical reasons) in certain circumstances it may be prudent to isolate animals showing signs of disease to reduce the risk of them infecting their cage mates that may have resolved the infection after medical countermeasure At the end of study all surviving mice underwent a terminal blood collection and the sera were assayed by ELISA using irradiated B. pseudomallei as the capture antigen.…”

“…Most patients have coexisting risk factors for the disease including diabetes, excessive alcohol use, chronic lung or renal disease, and other immunocompromising conditions (Currie et al, 2010;Currie, 2015;Limmathurotsakul et al, 2016;Dance and Limmathurotsakul, 2018;Wiersinga et al, 2018;Kaewrakmuk et al, 2023). Several animal models have been developed to study the pathogenesis of melioidosis (Leakey et al, 1998;Conejero et al, 2011;Limmathurotsakul et al, 2015;Welkos et al, 2015;Amemiya et al, 2017;Bearss et al, 2017;Trevino et al, 2018;Trevino et al, 2021;Nelson et al, 2023). The BALB/c is a highly susceptible strain of mice and is typically used to model acute melioidosis; in contrast, the C57BL/6 mouse strain is significantly more resistant, representing a more chronic model of disease which is often used for vaccine evaluation (Leakey et al, 1998;Tan et al, 2008;Lever et al, 2009;Srisurat et al, 2010;Conejero et al, 2011;Massey et al, 2014;Amemiya et al, 2017;Bearss et al, 2017;Trevino et al, 2018;Funnell et al, 2019;Nelson et al, 2023).…”

“…Several animal models have been developed to study the pathogenesis of melioidosis (Leakey et al, 1998;Conejero et al, 2011;Limmathurotsakul et al, 2015;Welkos et al, 2015;Amemiya et al, 2017;Bearss et al, 2017;Trevino et al, 2018;Trevino et al, 2021;Nelson et al, 2023). The BALB/c is a highly susceptible strain of mice and is typically used to model acute melioidosis; in contrast, the C57BL/6 mouse strain is significantly more resistant, representing a more chronic model of disease which is often used for vaccine evaluation (Leakey et al, 1998;Tan et al, 2008;Lever et al, 2009;Srisurat et al, 2010;Conejero et al, 2011;Massey et al, 2014;Amemiya et al, 2017;Bearss et al, 2017;Trevino et al, 2018;Funnell et al, 2019;Nelson et al, 2023). By varying the dose of B. pseudomallei delivered by aerosolization (a relevant route when evaluating countermeasures for public health or biodefense purposes), both acute and more protracted models of disease have been modelled in BALB/c mice (Srisurat et al, 2010;Bearss et al, 2017;Funnell et al, 2019).…”