Biomolecules capturing live bacteria from clinical samples.

Rapid phenotypic antimicrobial susceptibility testing (AST) requires the enrichment of live bacteria from patient samples, which is particularly challenging in the context of life-threatening bloodstream infections (BSIs) due to low bacterial titers. Over two decades, an extensive array of pathogen-specific biomolecules has been identified to capture live bacteria. The prevailing biomolecules are immune proteins of the complement system, antibodies, aptamers, phage proteins, and antimicrobial peptides. These biomolecules differ by their binder generation technologies and exhibit highly variable specificities, ranging from bacterial strains to most pathogenic bacteria. Here, we summarize how these diverse biomolecules were identified, list examples of successfully reported capture assays, and provide an outlook on the use of nanobodies raised against conserved surface-accessible proteins as promising biomolecules for pathogen capture.