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.

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