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Updated: Jun 10, 2026

Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
An ubiquitous antibacterial toxin from human gut bacteria engenders neonatal colonization advantage
Ezequiel Valguarnera1, Jessica Tung1, Jesse J Pak1
1Department of Pediatrics, Washington University, St. Louis, MO, USA.
Insights
The Type 6 Secretion System (T6SS) in Bacteroides fragilis, particularly the Bte3 toxin, plays a key role in early life gut colonization competition. This system helps strains dominate the gut environment unless competing bacteria have immunity to Bte3.
Area of Science:
- Microbiology
- Gut Microbiome Research
- Bacterial Pathogenesis
Background:
- Bacteroides fragilis is a dominant commensal in the human gut microbiome.
- The Type 6 Secretion System (T6SS) in B. fragilis is hypothesized to mediate inter-strain competition.
- Understanding T6SS function is crucial for comprehending gut microbial dynamics.
Purpose of the Study:
- To characterize the T6SS toxin repertoire in clinical isolates of B. fragilis.
- To investigate the role of the T6SS effector Bte3 in inter-strain competition during early life colonization.
- To explore the potential of T6SS diversity in shaping the gut microbiome.
Main Methods:
- Sequencing of nearly 900 clinical B. fragilis isolates.
- Characterization of T6SS effector repertoire, focusing on Bte3.
- In vitro intoxication assays with B. fragilis and Enterobacteriaceae.
- Murine model of neonatal gut colonization using T6SS-isogenic strains.
Main Results:
- Bte3 was identified as a prevalent T6SS effector.
- Bte3 demonstrated intoxication of B. fragilis and Enterobacteriaceae via a novel secretion mechanism.
- In vivo, Bte3-containing strains outcompeted susceptible B. fragilis strains in neonates.
- Strain displacement was dependent on the target strain's immunity to Bte3.
Conclusions:
- T6SS diversity, particularly Bte3, significantly influences B. fragilis early life colonization and competition.
- The potency and specificity of T6SS effectors shape the gut microbial landscape.
- This research offers insights for designing microbial interventions for neonatal gut commensal acquisition.
Abstract:
Bacteroides fragilis is a common member of the human colonic microbiota. In children, the B. fragilis Type 6 Secretion System (T6SS) has been suggested to mediate dominance between coexisting strains. We sequenced nearly 900 clinical isolates and characterized their T6SS toxin repertoire. The T6SS effector Bte3 was identified as one of the most prevalent effectors within this human isolate cohort. Bte3 exhibited the ability to intoxicate both B. fragilis and Enterobacteriaceae in vitro, and was defined as a periplasmic-intoxicating effector that employs previously unknown adaptor proteins for its secretion. The role of bte3 in early life competition was interrogated via a murine model in which neonates were exposed upon birth to two T6SS-isogenic strains. We observed that T6SS-engineered strains and human isolates containing bte3-based toxin combinations displaced competing B. fragilis strains unless these strains manifest immunity to bte3. These studies suggest that the landscape of T6SS effectors in the human population may be shaped not only by temporal exposure to distinct strains, but by potency of effector function. Our work underscores the relevance of T6SS diversity in B. fragilis early life competition and provides a potential roadmap to design microbial interventions in the context of neonatal acquisition of colonic commensals.
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