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The Impact of Age and Sex on Mouse Models of Melioidosis
Christopher P Klimko1, Sylvia R Treviño1, Alicia M Moreau2
1United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.
Abstract:
Mouse models have been used to generate critical data for many infectious diseases. In the case of Burkholderia pseudomallei, mouse models have been invaluable for bacterial pathogenesis studies as well as for testing novel medical countermeasures including both vaccines and therapeutics. Mouse models of melioidosis have also provided a possible way forward to better understand the chronicity associated with this infection, as it appears that BALB/c mice develop an acute infection with B. pseudomallei, whereas the C57BL/6 model is potentially more suggestive of a chronic infection. Several unanswered questions, however, persist around this model. In particular, little attention has been paid to the effect of age or sex on the disease outcome in these animal models. In this report, we determined the LD50 of the B. pseudomallei K96243 strain in both female and male BALB/c and C57BL/6 mice in three distinct age groups. Our data demonstrated a modest increase in susceptibility associated with sex in this model, and we documented important histopathological differences associated with the reproductive systems of each sex. There was a statistically significant inverse correlation between age and susceptibility. The older mice, in most cases, were more susceptible to the infection. Additionally, our retrospective analyses suggested that the impact of animal supplier on disease outcome in mice may be minimal. These observations were consistent regardless of whether the mice were injected with bacteria intraperitoneally or if they were exposed to aerosolized bacteria. All of these factors should be considered when designing experiments using mouse models of melioidosis.
Insights
Age and sex influence susceptibility in mouse models of melioidosis. Older mice showed increased susceptibility, and sex-linked differences were observed, impacting disease outcomes in both BALB/c and C57BL/6 strains.
Area of Science:
- Infectious Diseases
- Animal Models
- Bacteriology
Background:
- Mouse models are crucial for studying infectious diseases like melioidosis, caused by *Burkholderia pseudomallei*.
- Different mouse strains (BALB/c, C57BL/6) exhibit distinct infection dynamics (acute vs. chronic).
- The influence of age and sex on melioidosis disease outcomes in mouse models remains under-explored.
Purpose of the Study:
- To investigate the impact of age and sex on the susceptibility of BALB/c and C57BL/6 mice to *Burkholderia pseudomallei*.
- To determine the LD50 of *B. pseudomallei* K96243 across different age and sex groups.
- To identify potential histopathological differences related to sex in infected mice.
Main Methods:
- Determined the LD50 of *B. pseudomallei* K96243 in female and male BALB/c and C57BL/6 mice across three age groups.
- Performed histopathological examinations focusing on reproductive systems.
- Conducted retrospective analyses on the impact of animal supplier and administration route (intraperitoneal vs. aerosol).
Main Results:
- A modest increase in susceptibility was associated with sex, with notable histopathological differences in reproductive systems.
- A statistically significant inverse correlation between age and susceptibility was observed; older mice were generally more susceptible.
- Retrospective analyses indicated a minimal impact of animal supplier on disease outcome.
- Findings were consistent across both intraperitoneal injection and aerosol exposure routes.
Conclusions:
- Age and sex are significant factors influencing melioidosis outcomes in mouse models.
- Older mice, particularly in certain sex/strain combinations, exhibit increased susceptibility.
- These variables must be considered when designing experiments using mouse models for melioidosis research.
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