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Engineering Mycoplasma pneumoniae to bypass the association with Guillain-Barré syndrome

Alicia Broto1, Carlos Piñero-Lambea2, Carolina Segura-Morales1

  • 1Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain.

Microbes and Infection
|April 28, 2024
PubMed

Insights

Researchers engineered Mycoplasma pneumoniae strains to reduce Guillain-Barré syndrome (GBS) risk. Modified strains showed decreased antibody recognition, suggesting potential for safer live biotherapeutic products (LBPs) against respiratory diseases.

Area of Science:

  • Microbiology
  • Immunology
  • Biotechnology

Background:

  • Mycoplasma pneumoniae is a chassis for live biotherapeutic products (LBPs) for respiratory diseases.
  • Prior M. pneumoniae infections are linked to Guillain-Barré syndrome (GBS), raising safety concerns for M. pneumoniae-based LBPs.
  • Galactolipids, particularly galactocerebroside (GalCer), are implicated as M. pneumoniae antigens triggering GBS-associated autoimmune responses.

Purpose of the Study:

  • To engineer M. pneumoniae strains lacking galactolipid biosynthesis genes.
  • To assess the immunogenic potential of engineered strains using sera from GBS patients.
  • To identify M. pneumoniae strains suitable as GBS-free chassis for LBPs.

Main Methods:

  • Generation of M. pneumoniae mutant strains deficient in galactolipid biosynthesis.
  • Glycolipid profiling of engineered strains to confirm galactolipid absence.
  • Cross-reactivity assays using GBS patient sera against engineered M. pneumoniae strains.

Main Results:

  • Several engineered strains completely lacked galactolipids.
  • Certain mutant strains demonstrated reduced antibody recognition by GBS patient sera.
  • Correlation analysis indicated that factors beyond GalCer, such as ceramide levels and other glycolipids (DHCer, DGDAG), influence sera recognition.

Conclusions:

  • Engineered M. pneumoniae strains with reduced galactolipid content show promise for safer LBPs.
  • Further investigation into other contributing factors like ceramides and specific glycolipids is warranted.
  • Candidate GBS-free Mycoplasma chassis were identified for future LBP development.
Keywords:
GalactocerebrosidesGlycolipidsGlycosyltransferasesImmune responseMolecular mimicryMycoplasma pneumoniae

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