The Impact of Age and Sex on Mouse Models of Melioidosis
Christopher P. Klimko,
Sylvia R. Treviño,
Alicia M. Moreau,
Michael J. Aponte Cuadrado,
Joshua R. Meyer,
David P. Fetterer,
Susan L. Welkos,
Patricia L. Worsham,
Norman Kreiselmeier,
Carl Soffler,
Christopher K. Cote
Affiliations
Christopher P. Klimko
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Sylvia R. Treviño
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Alicia M. Moreau
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Pathology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Michael J. Aponte Cuadrado
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Joshua R. Meyer
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
David P. Fetterer
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Biostatistics Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Susan L. Welkos
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Patricia L. Worsham
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Norman Kreiselmeier
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Pathology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Carl Soffler
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Christopher K. Cote
United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Bacteriology Division 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
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.
