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Galactocerebroside biosynthesis pathways of Mycoplasma species: an antigen triggering Guillain-Barré-Stohl syndrome
Erika Gaspari1, Jasper J Koehorst1, Joachim Frey2
1Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Wageningen, the Netherlands.
Abstract:
Infection by Mycoplasma pneumoniae has been identified as a preceding factor of Guillain-Barré-Stohl syndrome. The Guillain-Barré-Stohl syndrome is triggered by an immune reaction against the major glycolipids and it has been postulated that M. pneumoniae infection triggers this syndrome due to bacterial production of galactocerebroside. Here, we present an extensive comparison of 224 genome sequences from 104 Mycoplasma species to characterize the genetic determinants of galactocerebroside biosynthesis. Hidden Markov models were used to analyse glycosil transferases, leading to identification of a functional protein domain, termed M2000535 that appears in about a third of the studied genomes. This domain appears to be associated with a potential UDP-glucose epimerase, which converts UDP-glucose into UDP-galactose, a main substrate for the biosynthesis of galactocerebroside. These findings clarify the pathogenic mechanisms underlining the triggering of Guillain-Barré-Stohl syndrome by M. pneumoniae infections.
Insights
Mycoplasma pneumoniae infection can trigger Guillain-Barré-Stohl syndrome by producing galactocerebroside. Researchers identified a specific protein domain in Mycoplasma species linked to this crucial biosynthesis pathway.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Mycoplasma pneumoniae infection is a known precursor to Guillain-Barré-Stohl syndrome.
- Guillain-Barré-Stohl syndrome results from an immune response targeting major glycolipids.
- M. pneumoniae is suspected to trigger this syndrome via galactocerebroside production.
Purpose of the Study:
- To investigate the genetic basis of galactocerebroside biosynthesis in Mycoplasma species.
- To identify specific genetic determinants responsible for M. pneumoniae's role in Guillain-Barré-Stohl syndrome.
Main Methods:
- Comparative genomics of 224 genome sequences from 104 Mycoplasma species.
- Utilized Hidden Markov models to analyze glycosyltransferases.
- Identified a specific protein domain (M2000535) associated with galactocerebroside biosynthesis.
Main Results:
- A functional protein domain, M2000535, was identified in approximately one-third of studied Mycoplasma genomes.
- This domain is linked to a potential UDP-glucose epimerase, crucial for UDP-galactose production.
- UDP-galactose is a key substrate for galactocerebroside biosynthesis.
Conclusions:
- The study elucidates the genetic mechanisms behind M. pneumoniae-induced Guillain-Barré-Stohl syndrome.
- Identified a specific protein domain (M2000535) as a key factor in the pathogenic pathway.
- Findings clarify how M. pneumoniae infection triggers Guillain-Barré-Stohl syndrome through galactocerebroside production.
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