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
BioMérieux, Open Innovation & Partnerships, 38390 La Balme Les Grottes, France.
Biomode, 4715-330 Braga, Portugal.
Diagnostics (Basel). 2021 Jul 14;11(7):1259. doi: 10.3390/diagnostics11071259.
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.
传染病是对健康的一种生存威胁，新出现和再次出现的病毒以及细菌抗生素耐药性的增加使这种威胁进一步加剧。传染病的靶向治疗需要精确诊断，尤其是在抗生素等广谱治疗方法无效的情况下。因此，越来越需要新的方法来开发灵敏且特异的体外诊断（IVD）检测。需要基础科学和转化研究来确定关键的微生物分子作为诊断靶点，确定相关的宿主对应物，并将这些知识用于开发或改进IVD。在这方面，一个被忽视的特征是病原体特异性粘附宿主细胞和组织的能力。与病原体-表面相互作用相关的分子实体就是所谓的粘附素。粘附素从蛋白质化合物到与真核宿主细胞基质分子和受体相互作用的（多）糖或脂质结构各不相同。这种相互作用共同决定了诊断检测的特异性和灵敏度。目前，粘附素-受体结合通常用于IVD检测的分析前阶段，重点是病原体富集。在当前高通量“组学”技术的支持下，对粘附素-配体相互作用的进一步探索可能会催生新一代广泛适用的病原体检测和表征工具。本综述描述了新型结构定义技术的最新成果，这些技术能够对粘附素、其受体和复合物进行详细的分子分析。由于宿主配体进化缓慢，相应的粘附素相互作用受到选择压力，以维持恒定的受体结合域。IVD应利用此类保守的结合位点，特别是利用人类配体来富集病原体。我们提供了一份基于粘附因子和病原体附着机制的方法清单，这些方法也可能与当前出现的病原体相关，包括2019冠状病毒病的病原体严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。
