Maltose and Maltodextrin Utilization by Listeria monocytogenes Depend on an Inducible ABC Transporter which Is Repressed by Glucose

Abstract

BackgroundIn the environment as well as in the vertebrate intestine, Listeriae have access to complex carbohydrates like maltodextrins. Bacterial exploitation of such compounds requires specific uptake and utilization systems.Methodology/Principal FindingsWe could show that Listeria monocytogenes and other Listeria species contain genes/gene products with high homology to the maltodextrin ABC transporter and utilization system of B. subtilis. Mutant construction and growth tests revealed that the L. monocytogenes gene cluster was required for the efficient utilization of maltodextrins as well as maltose. The gene for the ATP binding protein of the transporter was located distant from the cluster. Transcription analyses demonstrated that the system was induced by maltose/maltodextrins and repressed by glucose. Its induction was dependent on a LacI type transcriptional regulator. Repression by glucose was independent of the catabolite control protein CcpA, but was relieved in a mutant defective for Hpr kinase/phosphorylase.Conclusions/SignificanceThe data obtained show that in L. monocytogenes the uptake of maltodextrin and, in contrast to B. subtilis, also maltose is exclusively mediated by an ABC transporter. Furthermore, the results suggest that glucose repression of the uptake system possibly is by inducer exclusion, a mechanism not described so far in this organism.

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

“…This class of imaging agents can therefore be used to image bacterial biofilm infections. Although there has been a report on the use of 18 F-FDG to image S. aureus biofilms in mice (26), the use of 6$-18 F-fluoromaltotriose would enable imaging the biofilm infection rather than the surrounding inflammation. Bacterial biofilms have been implicated in the pathogenesis of a wide variety of chronic infections, particularly in patients who have had surgical implants or prosthetics (27).…”

“…The use of 67 Ga-citrate, 18 F-FDG, and labeled leukocytes has been well documented (6)(7)(8). Unfortunately, none of these tracers are specific for bacteria and are therefore unable to distinguish bacterial infection from sterile inflammation.…”

“…Extensively studied in E. coli, this transporter system has been shown to be present in many bacterial species, both gram-positive and gram-negative, including Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis, Listeria monocytogenes, and Vibrio cholera (17). The maltodextrin transporter has also been implicated in the virulence mechanisms of some of these pathogens (18)(19)(20)(21). The transporter is a complex of 5 proteins with the outer membrane maltoporin (LamB) and the periplasmic maltose binding protein (MalE) serving as the key determinants of transporter specificity (17).…”

“…Both our prior study and the work from Murthy et al demonstrated that this class of tracers was not only specific for bacteria but also could accurately distinguish infection from sterile inflammation. However, both 6-18 F-fluoromaltose and MH 18 F suffered from suboptimal pharmacokinetics and had poor signal-to-noise ratios, particularly in the thoracic region, which would preclude the use of these tracers for many clinical indications including lung and cardiac infections. In an effort to clinically translate this class of tracers, we have developed an improved second-generation tracer, 6$-18 F-fluoromaltotriose, building on the same scaffold.…”

“…In this study, we demonstrate that 6$-18 F-fluoromaltotriose is taken up by a variety of pathogenic bacterial strains in vitro and in vivo and that its pharmacokinetic profile is superior to the previously characterized probes for the maltodextrin transporter. 18 F-fluoride ion in dimethyl formamide (1 mL) at 85°C for 10 min. After being cooled to room temperature, 10 mL of water were added and the solution passed through a light C-18 Sep-pack cartridge (Water) and the crude protected 6$-18 F-fluoromaltotriose removed by passing 3 mL of acetonitrile through the cartridge.…”