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Publication . Preprint . Article . 2019

Pseudomonas aeruginosa lectin LecB impairs keratinocyte fitness by abrogating growth factor signalling

Alessia Landi; Muriel Mari; Tobias Wolf; Svenja Kleiser; Christine Gretzmeier; Isabel Wilhelm; Dimitra Kiritsi; +6 Authors
Open Access
Published: 15 Nov 2019 Journal: Life Science Alliance, volume 2, issue 6 (eissn: 2575-1077, Copyright policy )
Publisher: Life Science Alliance LLC
Country: Netherlands

Lectins are glycan-binding proteins with no catalytic activity and ubiquitously expressed in nature. Numerous bacteria use lectins to efficiently bind to epithelia, thus facilitating tissue colonisation. Wounded skin is one of the preferred niches for Pseudomonas aeruginosa, which has developed diverse strategies to impair tissue repair processes and promote infection. Here, we analyse the effect of the P. aeruginosa fucose-binding lectin LecB on human keratinocytes and demonstrate that it triggers events in the host, upon binding to fucosylated residues on cell membrane receptors, which extend beyond its role as an adhesion molecule. We found that LecB associates with insulin-like growth factor-1 receptor and dampens its signalling, leading to the arrest of cell cycle. In addition, we describe a novel LecB-triggered mechanism to down-regulate host cell receptors by showing that LecB leads to insulin-like growth factor-1 receptor internalisation and subsequent missorting towards intracellular endosomal compartments, without receptor activation. Overall, these data highlight that LecB is a multitask virulence factor that, through subversion of several host pathways, has a profound impact on keratinocyte proliferation and survival.

This study provides a novel function of the bacterial lectin LecB, which dampens cell proliferation and survival by targeting the insulin-like growth factor-1 for degradation, without receptor activation.

Subjects by Vocabulary

Microsoft Academic Graph classification: Endosome Growth factor medicine.medical_treatment medicine Chemistry Receptor Cell cycle Plasma protein binding Keratinocyte medicine.anatomical_structure Cell biology Intracellular Cell membrane Virulence factor Growth factor receptor


Research Article, Research Articles, 4, 16, Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology

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Funded by
NWO| A three-dimensional look into autophagy
  • Funder: Netherlands Organisation for Scientific Research (NWO) (NWO)
  • Project Code: 2300175771
The interactions of the Pseudomonas aeruginosa lectins LecA and LecB with glycosphingolipids result in membrane invagination, signaling and cellular uptake of the bacterium
  • Funder: European Commission (EC)
  • Project Code: 282105
  • Funding stream: FP7 | SP2 | ERC
Protecting patients with enhanced susceptibility to infections
  • Funder: European Commission (EC)
  • Project Code: 713660
  • Funding stream: H2020 | MSCA-COFUND-DP
Driving next generation autophagy researchers towards translation
  • Funder: European Commission (EC)
  • Project Code: 765912
  • Funding stream: H2020 | MSCA-ITN-ETN
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Preprint . 2019