Role of ST6GAL1 and ST6GAL2 in subversion of cellular signaling during enteroaggregative Escherichia coli infection of human intestinal epithelial cell lines

Abstract Emerging evidence have suggested that aberrant sialylation on cell-surface carbohydrate architecture may influence host–pathogen interactions. The α2,6-sialyltransferase (ST) enzymes were found to alter the glycosylation pattern of the pathogen-infected host cell-surface proteins, which could facilitate its invasion. In this study, we assessed the role of specific α2,6-ST enzymes in the regulation of enteroaggregative E. coli (EAEC)–induced cell signaling pathways in human intestinal epithelial cells. EAEC-induced expression of α2,6-ST family genes in HCT-15 and INT-407 cell lines was assessed at mRNA level by qRT-PCR. Specific esi-RNA was used to silence the target ST-gene in each of the EAEC-infected cell type. Subsequently, the role of these enzymes in regulation of EAEC-induced cell signaling pathways was unraveled by analyzing the expression of MAPkinases (ERK1/2, p38, JNK) and transcription factors (NFκB, cJun, cFos, STAT) at mRNA and protein levels by qRT-PCR and western immunoblotting, respectively, expression of selected sialoglycoproteins by western immunoblotting along with the secretory IL-8 response using sandwich ELISA. ST6GAL-1 and ST6GAL-2 were efficiently silenced in EAEC-infected HCT-15 and INT-407 cells, respectively. Significant reduction in EAEC-induced activation of MAPKs, transcription factors, sialoglycoproteins, and IL-8 secretion was noted in ST-silenced cells in comparison to the respective control cells. We propose that ST6GAL-1 and ST6GAL-2 are quintessential for EAEC-induced stimulation of MAPK-mediated pathways, resulting in activation of transcription factors, leading to an inflammatory response in the human intestinal epithelial cells. Our study may be helpful to design better therapeutic strategies to control EAEC- infection. Key points • EAEC induces α2,6-sialyltransferase (ST) upregulation in intestinal epithelial cells • Target STs (ST6GAL-1 & ST6GAL-2) were efficiently silenced using specific esiRNAs • Expression of MAPKs, transcription factors & IL-8 was reduced in ST silenced cells Graphical Abstract.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:107

Enthalten in:

Applied microbiology and biotechnology - 107(2023), 4 vom: 17. Jan., Seite 1405-1420

Sprache:

Englisch

Beteiligte Personen:

Chandel, Shipra [VerfasserIn]
Joon, Archana [VerfasserIn]
Kaur, Simarpreet [VerfasserIn]
Ghosh, Sujata [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

58.30$jBiotechnologie

42.30$jMikrobiologie

Themen:

Enteroaggregative
IL-8 secretion
P-3Fax-Neu5Ac
QRT-PCR
Sialyltransferases
Silencing

RVK:

RVK Klassifikation

Anmerkungen:

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s00253-022-12321-2

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2133752773

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