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Francisella tularensis Glyceraldehyde-3-Phosphate Dehydrogenase Is Relocalized during Intracellular Infection and Reveals Effect on Cytokine Gene Expression and Signaling
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SYSNO ASEP 0570267 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Francisella tularensis Glyceraldehyde-3-Phosphate Dehydrogenase Is Relocalized during Intracellular Infection and Reveals Effect on Cytokine Gene Expression and Signaling Author(s) Pávková, I. (CZ)
Kopečková, M. (CZ)
Link, M. (CZ)
Vlčák, Erik (UMG-J)
Filimonenko, Vlada (UMG-J) RID, ORCID
Lecová, L. (CZ)
Žáková, J. (CZ)
Lasková, P. (CZ)
Sheshko, V. (CZ)
Macháček, M. (CZ)
Stulík, J. (CZ)Number of authors 11 Article number 607 Source Title Cells. - : MDPI
Roč. 12, č. 4 (2023)Number of pages 22 s. Language eng - English Country CH - Switzerland Keywords multitasking ; pleiotropy ; Francisella ; glyceraldehyde-3-phosphate dehydrogenase ; infection ; secretion ; interacting partners OECD category Cell biology R&D Projects LM2018129 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF18_046/0016045 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001775 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000939293900001 EID SCOPUS 85148965551 DOI 10.3390/cells12040607 Annotation Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known for its multifunctionality in several pathogenic bacteria. Our previously reported data suggest that the GAPDH homologue of Francisella tularensis, GapA, might also be involved in other processes beyond metabolism. In the present study, we explored GapA's potential implication in pathogenic processes at the host cell level. Using immunoelectron microscopy, we demonstrated the localization of this bacterial protein inside infected macrophages and its peripheral distribution in bacterial cells increasing with infection time. A quantitative proteomic approach based on stable isotope labeling of amino acids in cell culture (SILAC) combined with pull-down assay enabled the identification of several of GapA's potential interacting partners within the host cell proteome. Two of these partners were further confirmed by alternative methods. We also investigated the impact of gapA deletion on the transcription of selected cytokine genes and the activation of the main signaling pathways. Our results show that increment gapA-induced transcription of genes encoding several cytokines whose expressions were not affected in cells infected with a fully virulent wild-type strain. That might be caused, at least in part, by the detected differences in ERK/MAPK signaling activation. The experimental observations together demonstrate that the F. tularensis GAPDH homologue is directly implicated in multiple host cellular processes and, thereby, that it participates in several molecular mechanisms of pathogenesis. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2024 Electronic address https://www.mdpi.com/2073-4409/12/4/607
Number of the records: 1