title: Ubiquitous detection of gram-positive bacteria with bioorthogonal magnetofluorescent nanoparticles.
abstract: The ability to rapidly diagnose gram-positive pathogenic bacteria would have far reaching biomedical and technological applications. Here we describe the bioorthogonal modification of small molecule antibiotics (vancomycin and daptomycin), which bind to the cell wall of gram-positive bacteria. The bound antibiotics conjugates can be reacted orthogonally with tetrazine-modified nanoparticles, via an almost instantaneous cycloaddition, which subsequently renders the bacteria detectable by optical or magnetic sensing. We show that this approach is specific, selective, fast and biocompatible. Furthermore, it can be adapted to the detection of intracellular pathogens. Importantly, this strategy enables detection of entire classes of bacteria, a feat that is difficult to achieve using current antibody approaches. Compared to covalent nanoparticle conjugates, our bioorthogonal method demonstrated 1-2 orders of magnitude greater sensitivity. This bioorthogonal labeling method could ultimately be applied to a variety of other small molecules with specificity for infectious pathogens, enabling their detection and diagnosis.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, Massachusetts 02114, USA.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Chung
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
authors.forename: Ghyslain
authors.initials: G
authors.lastname: Budin
authors.forename: Changwook
authors.initials: C
authors.lastname: Min
authors.forename: Monty
authors.initials: M
authors.lastname: Liong
authors.forename: David
authors.initials: D
authors.lastname: Issadore
authors.forename: Hakho
authors.initials: H
authors.lastname: Lee
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D034242:Cyclooctanes / Q000737:chemistry; D017576:Daptomycin / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006094:Gram-Positive Bacteria / Q000302:isolation & purification* / Q000378:metabolism; D042541:Intracellular Space / Q000382:microbiology; D059346:Magnets / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D014640:Vancomycin / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D034242:Cyclooctanes; D005456:Fluorescent Dyes; D014640:Vancomycin; D017576:Daptomycin