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Article Dans Une Revue Diagnostics Année : 2021

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

Alex van Belkum
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Carina Almeida
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Sounak Chowdhury
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Rucha Datar
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Ian Eastwood
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Manisha Goyal
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Lotta Happonen
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Volkhard a J Kempf
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Anchal Malik
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Ina Meuskens
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Paul A Milner
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Nicole Pamme
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Sally A Peyman
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Arno Thibau
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Diana J Vaca
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Dirk Linke
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Résumé

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.
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hal-03331223 , version 1 (01-09-2021)

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Alex van Belkum, Carina Almeida, Benjamin Bardiaux, Sarah V Barrass, Sarah J Butcher, et al.. Host-Pathogen Adhesion as the Basis of Innovative Diagnostics for Emerging Pathogens. Diagnostics, 2021, 11 (7), pp.1259. ⟨10.3390/diagnostics11071259⟩. ⟨hal-03331223⟩

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