Related Experiment Video
Updated: Jul 18, 2026
Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
fliP influences Citrobacter koseri macrophage uptake, cytokine expression and brain abscess formation in the neonatal
Abstract:
Citrobacter koseri causes neonatal meningitis frequently complicated with multiple brain abscesses. During C. koseri central nervous system infection in the neonatal rat model, previous studies have documented many bacteria-filled macrophages within the neonatal rat brain and abscesses. Previous studies have also shown that C. koseri is taken up by, survives phagolysosomal fusion and replicates in macrophages in vitro and in vivo. In this study, in order to elucidate genetic and cellular factors contributing to C. koseri persistence, a combinatory technique of differential fluorescence induction and transposon mutagenesis was employed to isolate C. koseri genes induced while inside macrophages. Several banks of mutants were subjected to a series of enrichments to select for gfp : : transposon fusion into genes that are turned off in vitro but expressed when intracellular within macrophages. Further screening identified several mutants attenuated in their recovery from macrophages compared with the wild-type. A mutation within an Escherichia coli fliP homologue caused significant attenuation in uptake and hypervirulence in vivo, resulting in death within 24 h. Furthermore, analysis of the immunoregulatory interleukin (IL)-10/IL-12 cytokine response during infection suggested that C. koseri fliP expression may alter this response. A better understanding of the bacteria-macrophage interaction at the molecular level and its contribution to brain abscess formation will assist in developing preventative and therapeutic strategies.
Insights
Citrobacter koseri persistence in macrophages is key to neonatal meningitis. Researchers identified a gene, fliP, crucial for bacterial survival and virulence, offering new therapeutic targets.
Area of Science:
- Infectious Diseases
- Microbiology
- Immunology
Background:
- Citrobacter koseri is a significant cause of neonatal meningitis, often leading to brain abscesses.
- C. koseri survives and replicates within macrophages, contributing to its persistence during central nervous system infections.
- Understanding the molecular mechanisms of C. koseri-macrophage interaction is crucial for developing effective treatments.
Purpose of the Study:
- To identify genetic factors enabling Citrobacter koseri persistence within macrophages.
- To elucidate the role of specific C. koseri genes in the host-pathogen interaction during meningitis.
- To investigate the impact of C. koseri gene expression on the host immune response.
Main Methods:
- Employed differential fluorescence induction and transposon mutagenesis to isolate C. koseri genes induced within macrophages.
- Screened mutant banks to identify genes expressed intracellularly but not in vitro.
- Assessed mutant recovery from macrophages and in vivo virulence in a neonatal rat model.
Main Results:
- Identified several C. koseri mutants with impaired recovery from macrophages.
- A mutation in an Escherichia coli fliP homologue resulted in attenuated uptake and hypervirulence, causing rapid mortality.
- C. koseri fliP expression appears to modulate the interleukin (IL)-10/IL-12 cytokine response.
Conclusions:
- The fliP gene is critical for C. koseri virulence and survival within macrophages.
- C. koseri actively manipulates the host immune response, specifically the IL-10/IL-12 balance.
- Targeting the bacteria-macrophage interaction offers potential strategies for preventing and treating C. koseri meningitis.
