DNA Inversion Regulates Outer Membrane Vesicle Production in Bacteroides fragilis

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Bacteroides fragilis, a key human gut microbe, modifies cell surface molecules through DNA inversion.
• Outer membrane vesicle (OMV) production is crucial for bacterial interactions and virulence.

Purpose of the Study:

• To investigate the role of DNA inversions in regulating OMV formation in Bacteroides fragilis.
• To understand the genetic control mechanisms governing OMV biogenesis and its relation to environmental stress.

Main Methods:

• Construction and analysis of BF2766 mutants with locked promoter configurations (IVp-I/IVp-II).
• Assessment of OMV production levels in different mutant strains.
• Evaluation of mutant resistance to bile and antimicrobial peptides (LL-37, human β-defensin 2).

Main Results:

• ON/ON promoter configuration (IVp-I/IVp-II) resulted in hypervesiculation.
• OFF/OFF, ON/OFF, and OFF/ON configurations produced minimal OMVs.
• Hypervesiculating ON/ON mutants displayed increased resistance to bile, LL-37, and human β-defensin 2.
• Exposure to bile induced a higher prevalence of the ON/ON genotype in wild-type B. fragilis.

Conclusions:

• Bacteroides fragilis utilizes DNA inversions at two promoter regions to control OMV formation in response to membrane stress.
• Regulated OMV production influences bacterial survival under challenging conditions.
• The precise mechanism linking the two invertible promoter regions requires further investigation.