Engineering Mycoplasma pneumoniae to bypass the association with Guillain-Barré syndrome
Broto, Alicia (Centre de Regulació Genòmica)
Piñero-Lambea, Carlos (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Segura-Morales, Carolina (Centre de Regulació Genòmica)
Tio-Gillen, Anne P. (Erasmus University Medical Centre)
Unger, Wendy W.J. (University Medical Centre. Department of Pediatrics)
Burgos Castellanos, Raül (Centre de Regulació Genòmica)
Mazzolini, Rocco (Centre de Regulació Genòmica)
Miravet-Verde, Samuel (Centre de Regulació Genòmica)
Jacobs, Bart C. (Erasmus MC University Medical Center Rotterdam)
Casas, Josefina (Institut de Química Avançada de Catalunya)
Huizinga, Ruth (Erasmus University Medical Centre)
Lluch-Senar, Maria (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Serrano, Luis (Centre de Regulació Genòmica)

Date:	2024
Abstract:	A non-pathogenic Mycoplasma pneumoniae -based chassis is leading the development of live biotherapeutic products (LBPs) for respiratory diseases. However, reports connecting Guillain-Barré syndrome (GBS) cases to prior M. pneumoniae infections represent a concern for exploiting such a chassis. Galactolipids, especially galactocerebroside (GalCer), are considered the most likely M. pneumoniae antigens triggering autoimmune responses associated with GBS development. In this work, we generated different strains lacking genes involved in galactolipids biosynthesis. Glycolipid profiling of the strains demonstrated that some mutants show a complete lack of galactolipids. Cross-reactivity assays with sera from GBS patients with prior M. pneumoniae infection showed that certain engineered strains exhibit reduced antibody recognition. However, correlation analyses of these results with the glycolipid profile of the engineered strains suggest that other factors different from GalCer contribute to sera recognition, including total ceramide levels, dihexosylceramide (DHCer), and diglycosyldiacylglycerol (DGDAG). Finally, we discuss the best candidate strains as potential GBS-free Mycoplasma chassis.
Grants:	European Commission 101020135 Agencia Estatal de Investigación PID2021-122341NB-I00 Agencia Estatal de Investigación CEX2020-001049-S Agencia Estatal de Investigación PTQ2020-011048
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Mycoplasma pneumoniae ; Glycolipids ; Galactocerebrosides ; Glycosyltransferases ; Immune response ; Molecular mimicry
Published in:	Microbes and Infection, Vol. 26, Issues 5-6 (July 2024) , art. 105342, ISSN 1769-714X

DOI: 10.1016/j.micinf.2024.105342
PMID: 38679229

12 p, 1.2 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles