Host-pathogen adhesion as the basis of innovative diagnostics for emerging pathogens

Alex van Belkum, Carina Almeida, Benjamin Bardiaux, Sarah V. Barrass, Sarah J. Butcher, Tuğçe Çaykara, Sounak Chowdhury, Rucha Datar, Ian Eastwood, Adrian Goldman, Manisha Goyal, Lotta Happonen, Nadia Izadi-Pruneyre, Theis Jacobsen, Pirjo H. Johnson, Volkhard A.J. Kempf, Andreas Kiessling, Juan Leva Bueno, Anchal Malik, Johan MalmströmIna Meuskens, Paul A. Milner, Michael Nilges, Nicole Pamme, Sally A. Peyman, Ligia R. Rodrigues, Pablo Rodriguez-Mateos, Maria G. Sande, Carla Joana Silva, Aleksandra Cecylia Stasiak, Thilo Stehle, Arno Thibau, Diana J. Vaca, Dirk Linke

Forskningsoutput: TidskriftsbidragÖversiktsartikelPeer review

Sammanfattning

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases re-quires precision diagnostics, especially in cases where broad-range therapeutics such as antibiotics fail. There is thus an increasing need for new approaches to develop sensitive and specific in vitro diagnostic (IVD) tests. Basic science and translational research are needed to identify key microbial molecules as diagnostic targets, to identify relevant host counterparts, and to use this knowledge in developing or improving IVD. In this regard, an overlooked feature is the capacity of pathogens to adhere specifically to host cells and tissues. The molecular entities relevant for pathogen–surface interaction are the so-called adhesins. Adhesins vary from protein compounds to (poly-)saccharides or lipid structures that interact with eukaryotic host cell matrix molecules and receptors. Such interactions co-define the specificity and sensitivity of a diagnostic test. Currently, adhesin-receptor binding is typically used in the pre-analytical phase of IVD tests, focusing on pathogen enrichment. Further exploration of adhesin–ligand interaction, supported by present high-throughput “omics” technolo-gies, might stimulate a new generation of broadly applicable pathogen detection and characterization tools. This review describes recent results of novel structure-defining technologies allowing for detailed molecular analysis of adhesins, their receptors and complexes. Since the host ligands evolve slowly, the corresponding adhesin interaction is under selective pressure to maintain a constant receptor binding domain. IVD should exploit such conserved binding sites and, in particular, use the human ligand to enrich the pathogen. We provide an inventory of methods based on adhesion factors and pathogen attachment mechanisms, which can also be of relevance to currently emerging pathogens, including SARS-CoV-2, the causative agent of COVID-19.

Originalspråkengelska
Artikelnummer1259
TidskriftDiagnostics
Volym11
Nummer7
DOI
StatusPublished - 2021 juli

Bibliografisk information

Funding Information:
The authors gratefully thank J?rgen Berger and Katharina Hipp (both Max Planck-Institute for Developmental Biology, T?bingen, Germany) for the electron microscopy dis-played in Figure 1.This research was funded by the European Union?s Horizon 2020 research and innovation program in a project named Viral and Bacterial Adhesin Network Training (ViBrANT) under Marie Sk?odowska-Curie Grant Agreement No. 765042. A.G. also acknowledges support from the BBSRC (grant number BB/M021610/1).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Ämnesklassifikation (UKÄ)

  • Mikrobiologi inom det medicinska området

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