Heterologous protein exposure and secretion optimization in Mycoplasma pneumoniae

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Ana, Yamile
  • dc.contributor.author Gerngross, Daniel
  • dc.contributor.author Serrano Pubull, Luis, 1982-
  • dc.date.accessioned 2025-01-31T07:54:16Z
  • dc.date.available 2025-01-31T07:54:16Z
  • dc.date.issued 2024
  • dc.description.abstract The non-pathogenic Mycoplasma pneumoniae engineered chassis (Mycochassis) has demonstrated the ability to express therapeutic molecules in vitro and to be effective for treatment of lung infectious diseases in in vivo mouse models. However, the expression of heterologous molecules, whether secreted or exposed on the bacterial membrane has not been optimized to ensure sufficient secretion and/or exposure levels to exert a maximum in vivo biological effect. Here, we have improved the currently used secretion signal from MPN142 protein. We found that mutations at P1' position of the signal peptide cleavage site do not abrogate secretion but affect it. Increasing hydrophobicity and mutations at the C-terminal of the signal peptide increases secretion. We tested different lipoprotein signal peptides as possible N-terminal protein anchoring motifs on the Mpn cell surface. Unexpectedly we found that these peptides exhibit variable retention and secretion rates of the protein, with some sequences behaving as full secretion motifs. This raises the question of the biological role of the lipobox motif traditionally thought to anchor membrane proteins without a helical transmembrane domain. These results altogether represent a step forward in chassis optimization, offering different sequences for secretion or membrane retention, which could be used to improve Mycochassis as a delivery vector, and broadening its therapeutic possibilities.
  • dc.description.sponsorship This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreements No 670216 and 101020135). We also acknowledge the support of the Spanish Ministry of Science, Innovation and Universities through the Plan Nacional PID2021-122341NB-I00 funded by MICIU/AEI/10.13039/501100011033/FEDER, UE.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Ana Y, Gerngross D, Serrano L. Heterologous protein exposure and secretion optimization in Mycoplasma pneumoniae. Microb Cell Fact. 2024 Nov 13;23(1):306. DOI: 10.1186/s12934-024-02574-z
  • dc.identifier.doi http://dx.doi.org/10.1186/s12934-024-02574-z
  • dc.identifier.issn 1475-2859
  • dc.identifier.uri http://hdl.handle.net/10230/69402
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Microb Cell Fact. 2024 Nov 13;23(1):306
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670216
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/101020135
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-122341NB-I00
  • dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.other Mycoplasma pneumoniae
  • dc.title Heterologous protein exposure and secretion optimization in Mycoplasma pneumoniae
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Center for Genomic Regulation (CRG))
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)