MoS₂-Modified Curcumin Nanostructures: The Novel Theranostic Hybrid Having Potent Antibacterial and Antibiofilm Activities against Multidrug-Resistant Hypervirulent Klebsiella pneumoniae

Abstract

The recent emergence of hypervirulent clinical variants of Klebsiella pneumoniae (hvKP) causing community-acquired, invasive, metastatic, life-threatening infections of lungs, pleura, prostate, bones, joints, kidneys, spleen, muscles, soft-tissues, skin, eyes, central nervous system (CNS) including extrahepatic abscesses, and primary bacteremia even in healthy individuals has posed stern challenges before the existing treatment modalities. There is therefore an urgent need to look for specific and effective therapeutic alternatives against the said bacterial infection or recurrence. A new type of MoS 2 -modified curcumin nanostructure has been developed and evaluated as a potential alternative for the treatment of multidrug-resistant isolates. The curcumin quantum particles have been fabricated with MoS 2 via a seed-mediated hydrothermal method, and the resulting MoS 2 -modified curcumin nanostructures (MQCs) have been subsequently tested for their antibacterial and antibiofilm properties against hypervirulent multidrug-resistant Klebsiella pneumoniae isolates. In the present study, we found MQCs inhibiting the bacterial growth at a minimal concentration of 0.0156 μg/mL, while complete inhibition of bacterial growth was evinced at concentration 0.125 μg/mL. Besides, we also investigated their biocompatibility both in vitro and in vivo. MQCs were found to be nontoxic to the SiHa cells at a dose as high as 1024 μg/ mL on the basis of the tested adhesion, spreading of the cells, and also on the various serological, biochemical, and histological investigations of the vital organs and blood of the Charles Foster Rat. These results suggest that MQCs have potent antimicrobial activities against hvKP and other drug resistant isolates and therefore may be used as broad spectrum antibacterial and antibiofilm agents.

Making of water soluble curcumin to potentiate conventional antimicrobials by inducing apoptosis-like phenomena among drug-resistant bacteria

“…We utilized the previously described method 19 . Multidrug-resistant clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa were treated with MIC concentration of sCur, vancomycin, and in combination (here data of only Klebsiella pneumoniae is shown).…”

“…We spectrophotometrically monitored the effect of sCur on growth rates of the respective bacterial isolates both in the presence and absence of the drugs as described previously 19 , 42 . Briefly, overnight grown bacterial cells were allowed to grow in the fresh BHI broth to their early exponential phase.…”

“…The comparative cytotoxicity of sCur and MoS 2 quantum dots were evaluated using HCT116 cells by measuring lactate dehydrogenase (LDH) activity as described earlier with modifications 19 , 46 . The two separate classes of test compounds were evaluated in concentration range 32, 64, 128, 256, 512, 1,024, and 2048 µg/ml.…”

“…Nevertheless, attempts have been made to increase its aqueous solubility and bioavailability by the nanoparticle-based approach producing micellar and lipid-drug hybrid nanoparticle formulations with improved water/plasma solubility 18 . Nonetheless, the innate toxicity issues cannot be overlooked 19 . The noncovalent formulation approach experiences other issues like limited transport of the micelles, slow drug release, and even leaching which jeopardize its use as frontline therapeutic agent 20 – 23 .…”

“…The noncovalent formulation approach experiences other issues like limited transport of the micelles, slow drug release, and even leaching which jeopardize its use as frontline therapeutic agent 20 – 23 . Even the quantum dots of curcumin are also reported which have shown improved stability, solubility, and therapeutic potential 6 , 19 , 24 . Apart from this, the attempt of covalent modification of one of the ketone groups in the β-diketone bridge of curcumin with phenyl hydrazine has also been made which resulted in a derivative of curcumin, CNB001.…”