Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity

Abstract

The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 10(5) colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.

Specific Imaging of Bacterial Infection Using 6″-18F-Fluoromaltotriose: A Second-Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria

“…As shown in Figure 2B, 6$-18 F-fluoromaltotriose can pick up as few as 10 6 CFUs of E. coli (infected tissues usually have 10 5 -10 6 CFUs of bacteria), with an improved signal-to-noise ratio as compared with the first-generation tracer 6-18 F-fluoromaltose (14). There is also evidence that tracers targeting the maltodextrin transporter can be taken up in S. aureus biofilms, as shown by Murthy et al (16). This class of imaging agents can therefore be used to image bacterial biofilm infections.…”

“…1; supplemental materials are available at http://jnm.snmjournals.org), a probe from a novel class of tracers targeting the maltodextrin transporter in bacteria (14,15). The concept of this class of tracers stems from an earlier study by Murthy et al, who showed that the maltodextrin transporter is unique to bacteria and that a fluorescently labeled maltohexose probe was able to image E. coli-induced myositis in rats (16). The maltose-maltodextrin transporter belongs to the adenosine triphosphate (ATP)-binding cassette (ABC) family of transporters.…”

Bacterial vectors for imaging and cancer gene therapy: a review

“…85,86 Maltodextrin-based optical imaging probes have been shown to successfully detect small numbers of bacteria in vivo with very high specificity and selectivity due to the fact that maltodextrin transporter is unique to bacteria. 87 A further advantage to this strategy is that the lumen of intestinal tissues and the skin are not permeable to glucose oligomers, and therefore MDPs delivered systemically should not be internalized by the resident bacterial microflora. Similarly, bis-zinc(II)-dicolylamide ligands have high affinity for the anionic phospholipids and other molecules residing in bacteria.…”

Bacteria-Targeting Conjugates Based on Antimicrobial Peptide for Bacteria Diagnosis and Therapy

“…Quantitative Counts of Neutrophils in the Whole Blood of the Mice Injected with NaCl, CAP, and CAP-UBI[29][30][31][32][33][34][35][36][37][38][39][40][41] …”