Page 100 - Annual report 2021-22

Annual Report 2021-22 |

Hemant K. Gautam

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Hemant K. Gautam’s lab works on targeting Cutibacterium acnes which is a Gram-positive bacterium
that forms part of the normal flora of the skin. Two approaches are being followed in his lab, one
based on photothermal therapy, and the other on targeting the lipolytic enzymes of the bacterium.

Photothermal therapy involves the use of a targeted 635nm laser assisted antibacterial therapy using
chitosan-coated Prussian Blue (CHPB) nanoparticles. This study reveals the increase in the therapeutic
efficacy of the photothermal Prussian blue core with careful surface modification with positively
charged chitosan molecules revealing the importance of interfacial potential and bacteria-targeting
capability of the nanostructures. Targeted PTT of CHPB nanobeads showed excellent inactivation
efficiency of 94.19% for Gram-negative bacterium Pseudomonas aeruginosa at 55 μg/ml and 97.70%
at 100 μg/ml for Gram-positive bacterium Staphylococcus aureus. In this project, biocompatible,
spherical shaped, photosensitizer-loaded chitosan coated Prussian blue nanoparticles were
synthesized. A biocompatible polymer chitosan was used as a protective matrix for the synthesis of
Prussian blue avoiding agglomeration and leading to a constrained environment to restrict the
nucleation and growth of the particle. The nanoparticles were characterised using dynamic light
scattering, electron microscopy and X-ray diffraction. EDX, TGA and XRD were performed for
composition and elemental analysis. CHPB-FD NPs showed higher antibacterial effect over PB NPs
owing to a combination of reasons, which includes higher affinity binding, inherent peroxidase-like
activity, and photothermal effect. These studies validate the importance of interfacial potential and
enhanced ROS generation due to the photothermal CHPB NPs in combination with photosensitizer,
contributing to growth inhibition in a concentration and time dependent manner. It can be concluded
that interactions at the nano-bio interface plays an important role in determining the antibacterial
propensity. CHPB NPs with positive surface charge and enhanced ablation effect of local hyperthermia
with a low power laser, shows great potential as a targeted photothermal nanoagent, opening up
future possibilities for the treatment of various bacterial infections.

Lipases are the main virulence factor in C. acnes that hydrolyse sebum lipid into free fatty acids that
are used as a carbon source by the bacterium. In this study, potential inhibitors against the C. acnes
lipase were identified via computational investigations. Molecular docking, MD simulations and
binding affinity analysis were performed between the active site of C. acnes lipase protein and
selected natural plant compounds. C. acnes lipase protein was downloaded from PDB and defined the
catalytically active site. Next, 16 active natural plant constituents were selected from the PubChem
library (based on their pharmacokinetics, pharmacodynamics, and Docking score). The five best active
compounds based upon docking score were prioritized. A 100 ns MD simulation run showed a stable
RMSD and less fluctuating RMSF graph with all five (luteonin, neryl-acetate, apigenin, orientin and
isotretinoin).

In collaboration with Navin Kumar Verma (Nanyang Technological University, Singapore) and
Kumutha Malar Vellasamy (University of Malaya, Malaysia), Hemant Gautam’s lab has initiated a new
study to target the cytokine storm in inflammatory conditions like COVID19. In this work, they propose
to generate inhalable gapmers targeting Toll-like receptors TLR7/8. Gapmers are chimeric antisense