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

Alessia Landi,Julie Claudinon,Dimitra Kiritsi,Roger Geiger,Alexander Nyström,Fulvio Reggiori,Winfried Römer,Christine Gretzmeier,Tobias Wolf,Isabel Wilhelm,Roland Thünauer,Muriel Mari,Svenja Kleiser

doi:10.26508/lsa.201900422

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.

Highlights

Bacteria can use many different strategies to infect host cells
We report that the P. aeruginosa lectin LecB is present in chronically infected human wounds, implying its contribution to the persistence of wound infections
We subsequently stained for LecB, and strikingly, we found that this lectin was distributed in the wound sections, both in the keratinocyte layers and in the dermis (Fig 1B)

Summary

Introduction

The initiation of an infection requires the recognition of specific structures at the host cell plasma membrane. This is often achieved by lectins, which bind to glycosylated residues on proteins and/or lipids present on the cell surface, mediating the attachment of the bacterium to the cell. Multivalency increases the binding affinity and specificity of the lectin–glycan interaction (Dam & Brewer, 2010). The binding of lectins to multiple cell surface receptors can induce receptor clustering and plasma membrane rearrangements, triggering their entry into the host (Romer et al, 2007; Windschiegl et al, 2009; Pezeshkian et al, 2017)

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