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Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens

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

Authors

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 Malmström

Ina Meuskens

Paul A. Milner

Michael Nilges

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



Abstract

Infectious diseases are an existential health threat, potentiated by emerging and re-emerging viruses and increasing bacterial antibiotic resistance. Targeted treatment of infectious diseases requires 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” technologies, 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.

Citation

van Belkum, A., Almeida, C., Bardiaux, B., Barrass, S. V., Butcher, S. J., Çaykara, T., …Linke, D. (2021). Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens. Diagnostics, 11(7), https://doi.org/10.3390/diagnostics11071259

Journal Article Type Article
Acceptance Date Jun 21, 2021
Online Publication Date Jul 14, 2021
Publication Date 2021-07
Deposit Date Jul 15, 2021
Publicly Available Date Jul 16, 2021
Journal Diagnostics
Print ISSN 2075-4418
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 11
Issue 7
Article Number 1259
DOI https://doi.org/10.3390/diagnostics11071259
Keywords Adhesin; Receptor; Infectious diseases; Diagnostics
Public URL https://hull-repository.worktribe.com/output/3804416
Publisher URL https://www.mdpi.com/2075-4418/11/7/1259

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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).





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