Attacking bacterial membrane: A novel approach for infection imaging

Abstract

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Objectives: Maltodextrin binding protein, a monomeric periplasmic binding protein, acts as the initial component of high-affinity active transport and bacterial chemotaxis. In MBP the maltosedextrin binding site is located at the base of the cleft between the two domains, identified as N & C domain. MBP binds and transport linear maltodextrins of up to seven glycosyl units. It has been shown that MBP can bind to cyclic maltodextrins such as α-cyclodextrin & β-cyclodextrin. Hydroxypropyl-β-cyclodextrin (HPCD), a chemically modified cyclodextrin, is preferred to natural cyclodextrins because of most extensive collection of safety data with no adverse reactions reported. These nonphysiological ligands are neither metabolized nor transported across the inner membrane nor do they induce any chemotactic response. We tried to exploit this property of β-CD for imaging infection.

Methods: The binding of β-HPCD to MBP of bacteria was demonstrated by computational method using Autodock programme in linux operating system. Crystallographic coordinates of MBP have been taken from the Brookhaven Protein Data Bank (pdb) and reference number is 1DMB. We had standardized the labeling protocol for β-HPCD with 99mTc.

Results: It has been demonstrated that β-HPCD-MBP interactions are established through hydrogen bonds and van der Waals interaction with the side chains of amino acid residues in MBP, which stabilize the interaction and keep the β-HPCD in the cleft of MBP. Following i.v., the 99mTc-HPCD bound in the cleft of the MBP of bacterial cell membrane present at the infection site & visualized in gamma camera.

Conclusions: The in silico & in vivo studies are well correlated. Thus 99mTc-HPCD could be used for infection imaging.