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Textbook procedures require the use of individual aptamers enriched in SELEX libraries which are subsequently chemically synthesized after their biochemical characterization. Here we show that this reduction of the available sequence space of large libraries and thus the diversity of binding molecules reduces the labelling efficiency and fidelity of selected single aptamers towards different strains of the human pathogen  Pseudomonas aeruginosa  compared to a polyclonal aptamer library enriched by a whole‐cell‐SELEX involving fluorescent aptamers. The library outperformed single aptamers in reliable and specific targeting of different clinically relevant strains, allowed to inhibit virulence associated cellular functions and identification of bound cell surface targets by aptamer based affinity purification and mass spectrometry. The stunning ease of this FluCell‐SELEX and the convincing performance of the  P. aeruginosa  specific library may pave the way towards generally new and efficient diagnostic techniques based on polyclonal aptamer libraries not only in clinical microbiology.

chemistry – a european journal

The Diversity of a Polyclonal FluCell‐SELEX Library Outperforms Individual Aptamers as Emerging Diagnostic Tools for the Identification of Carbapenem Resistant  Pseudomonas aeruginosa