Selective magnetic resonance imaging of antibiotic-resistant bacteria leveraging ATP-binding cassette sugar transporter-responsive probes

Current magnetic resonance imaging (MRI) methods often fail to differentiate bacterial infections from nonbacterial inflammatory conditions because of their poor specificity. To address this limitation, we synthesized two MRI probes that exploit bacterial-specific ATP-binding cassette (ABC) sugar transporters for the selective delivery of manganese porphyrin-based nanoparticles into antibiotic-resistant bacteria. These probes were synthesized via click chemistry by coupling azide-functionalized maltotriose with alkyne-modified manganese hematoporphyrin, which formed self-assembling nanoparticles. Our studies revealed ~ 65% probe uptake in gram-positive and gram-negative bacteria, with negligible uptake (~ 1%) in ABC transporter-deficient mutants. The probes demonstrated high longitudinal and transverse relaxivities (up to 11.56 mM⁻¹s⁻¹ and 102.0 mM⁻¹s⁻¹, respectively), enabling ultrasensitive MRI detection of human-derived methicillin-resistant Staphylococcus aureus and multidrug-resistant Escherichia coli at concentrations as low as 10⁶ CFU. In murine models, the probes differentiated bacterial nephritis from nonbacterial inflammation and visualized bacteria within tumour tissues, outperforming clinically used gadolinium-based agents. This study provides a promising approach for precise magnetic resonance imaging of antibiotic-resistant bacterial infections in deep tissues.