Fluorescent molecular probe for in vivo and in vitro targeting and imaging of an intracellular bacterial infection

Abstract

Intracellular bacterial infections are difficult to diagnose and treat because the host cells shelter the bacteria from molecular recognition by imaging agents, antibiotics, and the immune system. This problem arises when bladder epithelial cells are infected by uropathogenic Escherichia coli (UPEC)—one of the causative agents of urinary tract infection (UTI). UTIs are among the most common bacterial infections and a worldwide health concern. It is challenging to design molecular probes for intracellular UPEC imaging or targeted antibiotic treatment because the probe must possess multiple capabilities—it must permeate the host cell plasma membrane and selectively associate with the intracellular UPEC. Here, we report a “first-in-class” fluorescent probe called BactVue that is comprised of two structural components: a modified zinc(II)-2,2′-dipicolylamine complex (Zn-Oxy-DPA) as the bacteria targeting unit and an appended near-infrared cyanine fluorophore that is hydrophilic but with a near-neutral electrostatic charge. The unique capacity of BactVue to penetrate infected bladder cells and stain intracellular UPEC was demonstrated by a series of in vitro and in vivo fluorescence imaging studies, including a mouse model of UTI. The results support the feasibility of incorporating BactVue into diagnostic near-infrared fluorescence imaging methods that visualize the location of infected bladder cells during active UTI.