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

Current Microbiology
|January 25, 2008
PubMed

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.