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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 LU ; Datar, Rucha ; Eastwood, Ian and Goldman, Adrian , et al. (2021) In Diagnostics 11(7).
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 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.... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adhesin, Diagnostics, Infectious diseases, Receptor
in
Diagnostics
volume
11
issue
7
article number
1259
publisher
MDPI AG
external identifiers
  • scopus:85111128633
  • pmid:34359341
ISSN
2075-4418
DOI
10.3390/diagnostics11071259
language
English
LU publication?
yes
additional info
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.
id
829abed7-2d62-40d7-b1cc-31f569ef6795
date added to LUP
2021-08-07 16:54:29
date last changed
2024-06-15 13:58:26
@article{829abed7-2d62-40d7-b1cc-31f569ef6795,
  abstract     = {{<p>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.</p>}},
  author       = {{van Belkum, Alex and Almeida, Carina and Bardiaux, Benjamin and Barrass, Sarah V. and Butcher, Sarah J. and Çaykara, Tuğçe and Chowdhury, Sounak and Datar, Rucha and Eastwood, Ian and Goldman, Adrian and Goyal, Manisha and Happonen, Lotta and Izadi-Pruneyre, Nadia and Jacobsen, Theis and Johnson, Pirjo H. and Kempf, Volkhard A.J. and Kiessling, Andreas and Bueno, Juan Leva and Malik, Anchal and Malmström, Johan and Meuskens, Ina and Milner, Paul A. and Nilges, Michael and Pamme, Nicole and Peyman, Sally A. and Rodrigues, Ligia R. and Rodriguez-Mateos, Pablo and Sande, Maria G. and Silva, Carla Joana and Stasiak, Aleksandra Cecylia and Stehle, Thilo and Thibau, Arno and Vaca, Diana J. and Linke, Dirk}},
  issn         = {{2075-4418}},
  keywords     = {{Adhesin; Diagnostics; Infectious diseases; Receptor}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{MDPI AG}},
  series       = {{Diagnostics}},
  title        = {{Host-pathogen adhesion as the basis of innovative diagnostics for emerging pathogens}},
  url          = {{http://dx.doi.org/10.3390/diagnostics11071259}},
  doi          = {{10.3390/diagnostics11071259}},
  volume       = {{11}},
  year         = {{2021}},
}