publication . Article . 2019

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

Landi, Alessia; Mari, Muriel; Wolf, Tobias; Kleiser, Svenja; Gretzmeier, Christine; Wilhelm, Isabel; Kiritsi, Dimitra; Thünauer, Roland; Geiger, Roger; Nyström, Alexander; ...
Open Access English
  • Published: 15 Nov 2019 Journal: Life Science Alliance, volume 2, issue 6 (eissn: 2575-1077, Copyright policy)
  • Publisher: Life Science Alliance LLC
  • Country: Netherlands
Abstract
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.
Fields of Science and Technology classification (FOS)
01 natural sciences, 0104 chemical sciences, 010402 general chemistry, 03 medical and health sciences, 0303 health sciences, 030304 developmental biology
Subjects
free text keywords: Research Article, Research Articles, 4, 16, Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology, Growth factor, medicine.medical_treatment, medicine, Plasma protein binding, Cell cycle, Intracellular, Chemistry, Cell membrane, medicine.anatomical_structure, Receptor, Endosome, Keratinocyte, Cell biology, Virulence factor, Growth factor receptor
Communities
  • COVID-19
Funded by
NWO| A three-dimensional look into autophagy
Project
  • Funder: Netherlands Organisation for Scientific Research (NWO) (NWO)
  • Project Code: 2300175771
,
EC| PRONKJEWAIL
Project
PRONKJEWAIL
Protecting patients with enhanced susceptibility to infections
  • Funder: European Commission (EC)
  • Project Code: 713660
  • Funding stream: H2020 | MSCA-COFUND-DP
,
EC| DRIVE
Project
DRIVE
Driving next generation autophagy researchers towards translation
  • Funder: European Commission (EC)
  • Project Code: 765912
  • Funding stream: H2020 | MSCA-ITN-ETN
,
EC| LEC&LIP2INVADE
Project
LEC&LIP2INVADE
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
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