A low-cost strategy for the simple and rapid detection of bacterial cells in biological matrixes is presented herein. Escherichia coli and Salmonella typhimurium were chosen as model bacteria for the development of an electrochemical assay based on hollow AuAg nanoshells (NSs). By taking advantage of their electrocatalytic properties for the in situ generation of the electrochemical signal without the need of any other kind of reagent, substrate, or redox enzyme, high sensitivities (down to 10 2 CFU/mL) were achieved. Moreover, the recognition and discrimination of the model bacterial cells in the sample matrix was possible by relying solely on nonspecific affinity interactions between their cell walls and AuAg NSs surface, avoiding the use of expensive and fragile biological receptor. Compared to traditional, laboratorybased analytical tests available, this assay provides a promising proof-of-concept alternative that allows to obtain good sensitivities and selectivity in very short times in addition to the low cost.

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.