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A Murine Model of Group B Streptococcus Vaginal Colonization
Published on: November 16, 2016
Defensin susceptibility and colonization in the mouse model of AJ100, a polymyxin B-resistant, Brucella abortus RB51
Shirley M Halling1, Allen E Jensen, Steven C Olsen
1Bacterial Diseases of Livestock Unit, National Animal Disease Center, Agricultural Research Service, US Department of Agriculture, 2300 Dayton Avenue North, PO Box 70, Ames, IA 50010, USA. Shirley.Halling@ars.usda.gov
Abstract:
Intracellular pathogens selected for increased susceptibility to polycations are commonly attenuated, yet the effect of decreased susceptibility to polycations on pathogenicity has not been researched. The polymyxin-resistant mutant Brucella abortus AJ100 was characterized by comparing its susceptibility to the polycationic antibiotic polymyxin B, defensins, and lactoferricin, and its colonization and clearance in the mouse model to the parent strain RB51. MIC (minimum inhibitory concentration) values determined by Etest for AJ100 and RB51 were 1.5 and 0.25 mug/ml, respectively. Though AJ100 is less susceptible to polymyxin B than RB51, it was more susceptible than its parent strain to the cationic defensins melittin, magainin 2, and cecropin P1. In the mouse model, initial colonization of the spleen was lower for AJ100 than RB51, and the rate of clearance from the spleen was faster for AJ100 than RB51. However, initial colonization and clearance rates of AJ100 from the liver were indistinguishable from those of RB51. This study suggests that the susceptibility profile of Brucella to polycationic defensins rather than polymyxin B may be indicative of differential survival in the spleen and liver in the mouse and is indicative of spleen and liver residential macrophages' differing ability to inactivate Brucella.
Insights
Brucella abortus AJ100, a polymyxin-resistant mutant, showed reduced spleen colonization and faster clearance compared to its parent strain. This suggests defensin susceptibility, not polymyxin B resistance, impacts Brucella survival in mouse spleens.
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Intracellular pathogens attenuated by increased polycation susceptibility are common.
- The impact of decreased polycation susceptibility on pathogen pathogenicity remains understudied.
- Brucella abortus is an intracellular pathogen relevant to infectious disease research.
Purpose of the Study:
- To investigate the pathogenicity of a polymyxin-resistant Brucella abortus mutant (AJ100).
- To compare the susceptibility of AJ100 to polycationic antibiotics and defensins versus the parent strain (RB51).
- To evaluate the colonization and clearance dynamics of AJ100 in a mouse model.
Main Methods:
- Characterization of polymyxin B resistance in Brucella abortus AJ100 using Etest for minimum inhibitory concentration (MIC).
- Assessment of susceptibility to various cationic defensins (melittin, magainin 2, cecropin P1) and lactoferricin.
- In vivo studies using a mouse model to compare spleen and liver colonization and clearance rates between AJ100 and RB51.
Main Results:
- AJ100 exhibited significantly higher MIC values for polymyxin B (1.5 µg/ml) compared to RB51 (0.25 µg/ml).
- AJ100 showed increased susceptibility to cationic defensins melittin, magainin 2, and cecropin P1 compared to RB51.
- In mice, AJ100 displayed lower initial spleen colonization and faster spleen clearance rates than RB51; liver colonization and clearance were similar.
Conclusions:
- Brucella abortus susceptibility to defensins, rather than polymyxin B resistance, may predict differential survival in mouse spleen and liver.
- Macrophages in the spleen and liver exhibit varying capacities to inactivate Brucella.
- Polycation susceptibility profiles offer insights into pathogen-host interactions within specific organ environments.

