Mechanistic Insight into the Antibacterial Activity of Chitosan Exfoliated MoS₂ Nanosheets: Membrane Damage, Metabolic Inactivation, and Oxidative Stress

Abstract

Two-dimensional molybdenum disulfide (MoS2) based nanosheets functionalized or loaded with an antimicrobial agent have recently attracted attention as highly efficient antibacterial agent. MoS2 sheets act as the photothermal transducers in inducing bacterial cell death on impingement of NIR radiation or enabled cell inactivation by wrapping around the cells. However, the intrinsic ability of MoS2 to act as an effective antibacterial agent without the use of any external stimuli or antimicrobial agent is still not well explored. This study provides a detailed mechanism of antibacterial action of chitosan exfoliated MoS2 nanosheets (CS-MoS2) by deciphering the key events happening both at the membrane surface and inside the bacteria as a result of interaction of bacterial cells with the nanosheets. A simple, green, one-step process was employed for synthesizing stable and positively charged MoS2 nanosheets. The prepared nanosheets showed excellent bactericidal activity against both Gram-positive (MIC = 90 μg/mL, MBC = 120 μg/mL) and Gram-negative bacteria (MIC = 30 μg/mL, MBC = 60 μg/mL). Investigations into deciphering the mechanism of action revealed that the CS-MoS2 nanosheets interacted strongly with the bacterial cells through electrostatic interactions and caused rapid depolarization of the membranes through dent formations. On account of strong van der Waals and electrostatic forces occurring between the CS-MoS2 nanosheets and membrane phospholipid molecules, deepening of dents occurred, which resulted in complete membrane disruption and leakage of cytoplasmic contents. This led to inactivation of the bacterial respiratory pathway through inhibition of dehydrogenase enzymes and induced metabolic arrest in the cells. Simultaneously, disruption of the antioxidant defense system of the cells by increased levels of intracellular ROS subjected the cells to oxidative damage and added to the overall bactericidal action. The nanosheets also displayed antibiofilm properties and were found to be compatible with mammalian cells even at high concentrations.

Combating Actions of Green 2D-Materials on Gram Positive and Negative Bacteria and Enveloped Viruses

“…Apart from the extensive use of metal nanoparticles in antimicrobial studies, Gr and 2D TMDs have been widely studied so far to develop new technologies and novel antibacterial and antiviral nanocomposites to deal with the serious issues related to bacterial and viral infections. The considerable potential of MoS 2 NSs in various biomedical applications also grasps its key role in synergistic antibacterial and antiviral action on various pathogens ( Wu et al, 2016 ; Qu et al, 2017 ; Zhang et al, 2017 , 2018 , 2019 ; Kaur et al, 2018 ; Yuwen et al, 2018 ; Cao et al, 2019 ; Roy et al, 2019 ; Tang et al, 2020 ). The mechanism explained in the reported literature reveals a significant induction of physical damage and oxidative stress to the bacterial membrane which results in continuous disruption of bacterial cells and finally in cell death.…”

Two-dimensional nanomaterials beyond graphene for antibacterial applications: current progress and future perspectives

“…Here, we summarize several common 2D NBG-mediated synergistic antibacterial methods: (i) synergy of PTT with PDT 137-139; (ii) synergy of PTT with metallic ions release (Ag, Au, etc. ); (iii) synergy of chemotherapy with PTT 140; (iv) synergy of PTT with oxidative stress 79; (v) synergy of PTT with catalytic 139, 141-144; (vi) and tri-modal synergistic antibacterial 145, 146. At the same time, the synergetic antibacterial mechanism and application are detailedly discussed.…”

“…They found that the as-designed MoO 3-x -Ag killed pathogenic bacteria mainly through (i) photothermal effect of MoO 3-x nanosheets upon NIR irradiation; (ii) NIR light excitation of MoO 3-x -Ag trigger the release of Ag ions; and (iii) photocatalytic reaction. Moreover, Roy et al prepared chitosan exfoliated MoS 2 nanosheets (CS-MoS 2 ) and investigated their intrinsic antibacterial mechanism 146. They found that the CS-MoS 2 nanosheets could kill bacteria through a synergistic effect of ROS-dependent oxidative stress, physical contact caused membrane damage and metabolic inactivation.…”

Peroxidase-like behavior and photothermal effect of chitosan-coated Prussian-blue nanoparticles: dual-modality antibacterial action with enhanced bioaffinity

“…Similar observations with other nanoparticles have been reported in the literature. [32][33][34] Mechanistic study of photo induced antibacterial effect of the nanoparticles…”

“…31 Similar chitosan-coating strategies have been reported to enhance the antibacterial efficiency of several other nanoparticles, such as that of iron oxide and gold. [32][33][34] Chitosan is known to interact with the cyanoferrate groups on the PB surface to produce stable PB (core)/chitosan (shell) NPs, which have already been applied in several areas, such as electrocatalysis, photo-triggered gene delivery, photothermal therapy, etc. [35][36][37][38] We report for the first time the dual modality antibacterial application of CHPB NPs against both Gram-negative bacteria, Pseudomonas aeruginosa, and Gram-positive bacteria, Staphylococcus aureus.…”