Thursday, July 2 2020
14:00 - 15:00

IMSc Webinar

Synopsis Talk: Understanding the mechanical response of bacterial cell walls and cell membranes against antimicrobial agents

Garima Rani


Bacteria are single celled, prokaryotic micro-organisms that were one of the first life
forms to appear on earth and have since emerged as one of the most successful organisms
as well, populating habitats as diverse as hot springs, human gut, even radioactive waste. They have formed complex and varied associations with humans, which in several
instances has turned out to be beneficial for both. However, bacteria are also responsible
for causing several serious diseases in human beings, including tuberculosis, diptheria,
typhus, leprosy [2]. A crucial step in managing such bacterial infections has been the
development of antibiotics, which fight bacterial infections either by killing bacteria or
by slowing its growth, usually by impeding crucial cellular functions like cell wall synthesis and protein synthesis in the cell. However, several strains of bacteria have started
displaying an alarming rise in resistance to antibiotic treatment. This has rendered several
commonly used antibiotics largely ineffective. This necessitates the exploration and design of newer antibacterial agents. For this, an important pathway is to utilize biophysical methods to unravel the design principles of the bacterial cell and to model the action of anti-microbial agents on them, thus enabling us to effectively design and test the efficacy of new age antibacterials.

This Synopsis Talk is divided into two parts. In the first part, we study the design features
of the cell wall of bacteria, which is primarily composed of the peptidoglycan (PG)
network, a mesh of relatively long and stiff glycan chains, cross-linked intermittently by
flexible peptides. We explore the molecular scale architecture of the PG mesh and its
role in enhancing the toughness or the resistance to crack propagation, of the cell wall,
utilizing theoretical methods. We also investigate the effect of variability in the elastic
properties of the PG mesh on its bulk mechanical response, by studying an appropriately
modelled spring system using theoretical methods and simulations. In the second part of
the talk, we study the conformational landscape, aggregation dynamics and interactions
with model bacterial membrane of biomimetic antimicrobial polymers (AMPolys),
utilizing detailed atomistic molecular dynamics simulations. We specifically examine
the role played by neutral polar groups in influencing the aggregation dynamics of such
polymers in solution phase and study their membrane-interactions in depth. Further, we
also investigate the conformational landscape of AMPolys that have anionic functional
groups as constituents, with particular focus on probing the formation of salt bridges and
their role in determining the conformational dynamics of such polymers.

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