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A murine model for infection with Burkholderia cepacia with sustained persistence in the spleen
D P Speert1, B Steen, K Halsey
1Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4. speert@unixg.ubc.ca
Abstract:
Burkholderia cepacia is an opportunistic pathogen that causes severe systemic infections in patients with chronic granulomatous disease (CGD) or with cystic fibrosis (CF), but its mechanisms of virulence are poorly understood. We developed a murine model of systemic infection in wild-type (WT) and gamma interferon knockout (GKO) BALB/c mice to facilitate dissection of components of pathogenicity and host defense. Both WT and GKO mice were susceptible to chronic splenic infection with B. cepacia, but not with Pseudomonas aeruginosa. B. cepacia strains from patients with CGD persisted longer than those from CF patients. C57BL/6 mice were the most susceptible murine strain; bacteria persisted in the spleen for 2 months. DBA/2, BALB/c, and A/J strains of mice were relatively resistant to infection. Certain strains of B. cepacia complex can persist in the murine spleen after systemic infection; this may provide clues to its virulence in compromised hosts, such as those with CGD and CF.
Insights
Burkholderia cepacia persists in mice, offering insights into its virulence in patients with chronic granulomatous disease (CGD) and cystic fibrosis (CF). This opportunistic pathogen
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- * Burkholderia cepacia is an opportunistic pathogen causing severe infections in individuals with chronic granulomatous disease (CGD) and cystic fibrosis (CF).
- * The precise mechanisms underlying B. cepacia virulence remain incompletely understood.
- * Host immune responses play a critical role in controlling B. cepacia infections.
Purpose of the Study:
- * To establish and utilize a murine model to investigate the pathogenicity of B. cepacia.
- * To dissect the components of B. cepacia virulence and host defense mechanisms.
- * To understand the factors influencing B. cepacia persistence in vivo.
Main Methods:
- * Development of a systemic infection model in wild-type (WT) and gamma interferon knockout (GKO) BALB/c mice.
- * Inoculation with B. cepacia strains isolated from CGD and CF patients.
- * Comparative analysis of bacterial persistence in spleens of different mouse strains (C57BL/6, DBA/2, BALB/c, A/J).
Main Results:
- * Both WT and GKO mice exhibited susceptibility to chronic splenic infection with B. cepacia.
- * B. cepacia strains from CGD patients demonstrated longer persistence compared to those from CF patients.
- * C57BL/6 mice were the most susceptible strain, showing bacterial persistence for up to 2 months.
- * DBA/2, BALB/c, and A/J mice displayed relative resistance to B. cepacia infection.
Conclusions:
- * Certain B. cepacia complex strains can establish persistent splenic infections in mice.
- * The murine model effectively demonstrates B. cepacia persistence and differential susceptibility.
- * Findings provide potential insights into B. cepacia virulence in immunocompromised hosts like CGD and CF patients.
